bluuebunny/crossref_metadata_2025 huggingface dataset:
Common and distinct features of TIR domain function
Authors: Williams Simon , Alaidarous Mohammed , Ve Thomas , Zhang Xiaoxiao , Valkov Eugene , Bernoux Maud , Sohn Kee , Jones Jonathan , Dodds Peter , Kobe Bostjan
Published: November 2015

TIR (Toll/interleukin-1 receptor, resistance protein) domains feature in diverse proteins with functions in the immune system, such as animal TLRs (Toll-like receptors), plant NLRs (nucleotide binding, leucine-rich repeat) and bacterial virulence factors. It has been well established, especially through the work on TLRs, that signalling depends on regulated self-association of TIR domains. However, every single TIR domain structure has revealed a different association mode [1]. In the search for common features, we have targeted a number of TIR domains from mammals, plants and bacteria to characterize structurally. We have determined the crystal structures of the TIR domains from the human TLR adaptor protein MAL [1], the bacterial protein TcpB from Brucella melitensis [2] and the plant immune proteins L6 from flax [3] and SNC1, RPS4 and RRS1 from Arabidopsis (unpublished). In the case of the proteins RPS4 and RRS1, which work together as a protein complex to confer resistance to three different bacterial and fungal pathogens, we have determined, using linker-assisted crystallization, the first structure of a hetero-dimeric complex of TIR domains (Fig. 1). The association interface in this complex is conserved in the crystals of the TIR domains of RPS4 and RRS1 on their own, as well as in those of SNC1 and another Arabidopsis protein AT1G72930. Similarly, the dimerization interface observed in the structure of TcpB is conserved in the structure of the TIR domain-containing protein from Paracoccus denitrificans. We validated the association interfaces by site-directed mutagenesis coupled with a variety of cellular assays. As self-association is key to TIR domain function, our studies are finally revealing common features of the molecular function of TIR domains across phyla.
Structural characterization of the of inorganic and organic hydrotalcites
Authors: Palin Luca , Conterosito Eleonora , Milanesio Marco , Leoni Matteo , Koch Robert , Costantino Ferdinando , Perioli Luana , van Beek Wouter , Mugnaioli Enrico , Kolb Ute
Published: November 2015

Layered double hydroxides are versatile materials used for intercalating bioactive molecules, both in pharmaceutical and cosmetic fields, with the purpose of protecting them from degradation, enhancing their water solubility to increase bioavailability, and/or obtaining modified release properties. Hydrotalcite is commercially available in its carbonate form, which is usually transformed into the nitrate form and finally exchanged by organic anions to obtain or regulate bioactivity or photo-activity effects (1). In this study all the steps of these transformations were characterized from the structural viewpoints by X-ray powder diffraction (XRPD) and automated electron diffraction tomography (ADT). ADT allowed shedding light on the nitrate position and conformation inside LDH. XRPD demonstrated at first that the presence of carbonate impurities is able to drive the intercalation of organic molecules into LDH, since CO32- contaminated samples tend to assume d-spacings roughly multiple of LDH-CO3 d-spacing. Finally XRPD was employed at in situ conditions to unravel the structural transformation occurring during the substitution of carbonate by nitrate ion and of the nitrate ion by organic anions. The carbonate-nitrate substitutions resulted to be very rapid (only few seconds) and only the use of a fast area detector, coupled to synchrotron radiation, allowed obtaining reliable patterns to perform XRPD refinement of the disordered structure at the sub-second time resolution. The nitrate-organic substitution resulted slower and depending on the chemical properties of the organic molecules.
Structure Determination of New Phases K1.65V1.78W0.22O2(AsO4)2and K2V2O2(AsO4)2
Authors: Mezaoui Djillali , Belkhiri Sabrina , Belkhiri Thierry
Published: November 2015

Two new phases K1.65V1.78W0.22O2(AsO4)2 and K2V2O2(AsO4)2 [1,2] belonging to KTiOPO4 family (KTP) [3] have been synthesized and characterized by single crystal X-ray diffraction. The structure of K1.65V1.78W0.22O2(AsO4)2 shows an irregular MO6 octahedra (M=78%V+22%W) with two abnormal short bonds M–O (1.774 (7) Å) and (1.824 (8) Å) which suggest that the non linear optical property could be more important. In order to show the influence of the tungsten and vanadium on the distortion of the MO6 octahedra, we substituted the tungsten by the vanadium element. The single-crystal K2V2O2(AsO4)2 consists of common VO6 octahedra with one short bond V–O (1.652(2) Å) . We used SUPERFLIP and JANA 2006 programs [4, 5] to resolve and refine these structures. The refinement by JANA 2006 led to the reliability factors: (R =0.048, Rw = 0.064) for K1.65V1.78W0.22O2(AsO4)2, and (R =0.028, Rw = 0.034) for K2V2O2(AsO4). Structure of K1.65V1.78W0.22O2(AsO4)2 Structure of K2V2O2(AsO4)2 Space group: Pc21n Space group: Pc21n Cell parameters: Cell parameters: a = 6.5322 (7) Å a = 6.5368 (2) Å b = 10.7228 (9) Å b = 10.7228 (5) Å c = 13.0782 (5) Å c = 13.0666 (4) Å
Defect separation in strontium titanate: Formation of a polar phase
Authors: Hanzig Juliane , Zschornak Matthias , Mehner Erik , Hanzig Florian , Jachalke Sven , Nentwich Melanie , Stöcker Hartmut , Leisegang Tilmann , Röder Christian , Meyer Dirk
Published: November 2015

Stoichiometric perovskite-type strontium titanate acts as an insulator because of its wide electronic band gap and has therefore great potential as high-k dielectric and storage material in memory applications. Degradation phenomena of insulating properties of transition metal oxides occur during long time voltage application. From the defect chemistry point of view the question arises how mobile species react on an external electric field and which impact the redistribution has on the stability of the crystal structure. Here, we discuss near-surface reversible structural changes in SrTiO3 single crystals caused by oxygen vacancy redistribution in an external electric field. We present in-situ X-ray diffraction during and after electroformation. Several reflections are monitored and show a tetragonal elongation of the cubic unit cell. Raman investigations were carried out to verify that the expansion involves a transition from the centrosymmetric to a less symmetric structure. Regarding a whole formation cycle, two different time scales occur: a slow one during the increase of the lattice constant and a fast one after switching off the electric field. Based on the experimental data we suggest a model containing the formation of a polar SrTiO3 unit cell stabilized by the electric field, which is referred to as migration-induced field-stabilized polar phase [1] at room temperature. As expected by a non-centrosymmetric crystal structure, pyroelectric properties will be presented in conjunction with temperature modulated electroformation cycles. Furthermore, we show that intrinsic defect separation establishes a non-equilibrium accompanied by an electromotive force. A comprehensive thermodynamic deduction in terms of theoretical energy and entropy calculations indicates an exergonic electrochemical reaction after the electric field is switched off. Based on that driving force the experimental and theoretical proof of concept of a solid-state SrTiO3 battery is reported.
Interpreting the effect of de-solvation on structure of molecular crystals.
Authors: Chan Eric
Published: November 2015

The structure effects of varying hydration/solvation levels in molecular crystals can sometimes be difficult to characterize with analytical techniques based solely on Bragg diffraction or other more common methods such as thermal analysis or spectroscopy. It can be demonstrated that supplementary scattering features such as diffuse and satellite intensities can provide insight into these processes even just from a qualitative standpoint. Understanding the nature of these processes is of great importance to many industrial applications (e.g. pharmaceuticals, bulk characterization). One previous caveat is that interpretations for these features are often restricted to experts, yet our work demonstrates this is not the case. For our examples, real-space models can be used to calculate both diffuse diffraction and inter-modulation satellite features. In one case study what we observe when the water leaves the crystal is an incomplete phase transformation and each crystallite in the bulk can be explained as being made up of disordered layers of the different structure phases with an intermediate phase layer resulting in satellite reflections. Another example demonstrates how in a crystal which has one solvent replaced for another, temperature sensitive phase transitional phenomena are induced. Models based on disorder diffraction features not only provide further insight into understanding of the de-solvation process but also could account for observed changes in PXRD from bulk. This can be related to similar material behaviors observed in diffraction patterns from more complex host-guest systems.
Modulated order in ionic conductors: a fine line between helping and hindering
Authors: Ling Chris
Published: November 2015

"Solid-state ionic conduction relies on essentially conflicting structural properties: long-range crystalline order, to provide structural stability (as fuel cell membranes, battery cathodes etc.); and short-range disorder, to provide smooth conduction pathways without deep local energy minima that could trap the conducting species. Materials that combine these features are generally metastable, and prone to ordering into complex modulated structured that can only be described in (3+n) dimensions using the superspace formalism. Such ordering would normally be expected to seriously compromise conduction properties. However, low-temperature modulated structures can be effective and stable precursors to high-temperature ionic conductors - and, in some cases, can coexist with regions of local disorder that actually enhance conduction. The relationship between modulated order and ionic conduction is relatively little studied, but some of our recent work points to its potential importance. This presentation will focus on two examples: the (3+3)-dimensional commensurately modulated proton conductor Ba4Nb2O9.1/3H2O; [1,2] and the (3+3)-dimensional incommensurately modulated oxide ion conductor ""Type II"" Bi2O3.xNb2O5 (for which a single-crystal neutron diffraction pattern and the refined structure are shown below). [3] The aim is to show how modulated structures can be designed and manipulated to optimise technological performance by striking a balance between stabilising the overall framework while destabilising the conduction pathways."
The electronic and magnetic properties of strained La0.85Zr0.15MnO3films
Authors: Deshpande N. G. , Weng C. H. , Wang Y. F. , Shao Y. C. , Ling D. C. , Hsueh H. C. , Du C. H. , Pong W. F.
Published: November 2015

The electronic and magnetic properties of strained tetravalent-ion-doped La0.85Zr0.15MnO3 (LZMO) thin films that were epitaxially grown on SrTiO3 (STO) and MgO substrates were studied using temperature-dependent x-ray diffraction (XRD), x-ray absorption near-edge structure (XANES), x-ray linear dichroism (XLD) and x-ray magnetic circular dichroism (XMCD) at the Mn L3,2- and K-edge. XRD studies reveal that the LZMO thin films have compressive and tensile strains on the STO and MgO substrates, respectively. As temperature is reduced from room temperature to below magnetic transition temperature, the preferentially occupied Mn majority-spin eg orbital changes from the in-plane dx2-y2 to the out-of-plane d3z2-r2 orbital for LZMO/STO, and vice versa for LZMO/MgO. Experimental results suggest that the new hopping path that is mediated by the Mn2+ ions triggers a stronger d3z2-r2 orbital ordering of Mn3+ ions and enhances the ferromagnetic coupling between the Mn spin moments of t2g electrons in LZMO/STO, whereas the tensile strain stabilizes the dx2-y2 orbital by inducing lattice distortions of the MnO6 octahedra in LZMO/MgO.
High Energy Resolution X-ray Spectroscopy at SSRL and LCLS: Instruments and Applications
Authors: Sokaras Dimosthenis , Weng Tsu-Chien , Nordlund Dennis , Bergmann Uwe
Published: November 2015

High-resolution hard x-ray spectroscopies (XES, HERFD, RIXS, XRS) are now well-established characterization tools for providing insights of material's electronic and geometric structure. The high brilliance synchrotron radiation beamlines have made feasible the routine study of the electronic structure and ligand environment of metal coordination compounds and active centers in metalloproteins, electrochemical process under in-situ conditions, as well as studies on catalytic systems under ambient conditions. Moreover, the recent availability of Linac Coherent Light Source (LCLS), provides some unique opportunities for the study of ultrafast electronic structure dynamics in various phenomena such as electron transfer processes, transient molecular states, molecular dissociation, etc. At SLAC National Accelerator Laboratory we have developed recently a set of high-resolution x-ray spectroscopic capabilities based on various multicrystal spectrometers. At SSRL we have built three multicrystal Johann spectrometers enabling XES/RIXS/HERDF techniques as well as X-ray Raman Spectroscopy. For LCLS, we have developed an energy dispersive multicrystal von Hamos spectrometer that records simultaneously the overall emission spectrum, enabling shot-by-shot time-resolved studies. Representative examples of application will be shown and discussed from the ongoing spectroscopy programs of SSRL and LCLS.
X-ray Raman scattering spectroscopy
Authors: Huotari Simo
Published: November 2015

For elements with low atomic number, or shallow absorption edges falling in the energy range below ~1 keV, x-ray absorption studies are often limited by surface sensitivity and the necessity of a vacuum environment, making bulk-sensitive measurements and for example studies of liquids difficult. An exciting alternative is provided by X-ray Raman scattering (XRS) spectroscopy. It is used to measure a photon-in-photon-out process, where a hard x-ray photon loses only part of its energy creating an excitation of an inner core electron. As such, it is the x-ray analogue of electron energy loss spectroscopy. The advantage of XRS is that the incident photon energy can be chosen freely and thus low-energy absorption edges can be studied with high-energy X-rays. Thus XRS is becoming increasingly popular since it allows for bulk-sensitive measurements of inner core spectra where the corresponding x-ray absorption threshold falls into the soft x-ray regime. This lifts all constraints on the sample environment inherent to soft x-ray studies, and offers access to bulk-sensitive information on solids, liquids and gases as well as systems in enclosed sample environments such as high-pressure cells. For example the microscopic structure of water within the supercritical regime has been recently studied using the oxygen K-edge excitation spectra measured by XRS, yielding new information on the hydrogen-bond network of water in extreme conditions [1]. Another important feature of XRS is that it allows for other than dipole transitions to be studied, thanks to an practically unlimited range of momentum transfer offered by hard x-rays. These higher order multipole excitations can yield novel information on the electronic structure, not accessible by many other spectroscopies [2]. The availability of XRS instruments at third-generation synchrotron radiation sources has made highly accurate XRS measurements possible. XRS can be even used as a contrast mechanism in three-dimensional X-ray imaging [3]. In this contribution, the capabilities of XRS and recent examples of novel studies allowed by it will be reviewed.
TDP-43 domain assembly and RNA binding specificity
Authors: Yuan Hanna , Kuo Pan-Hsien , Chiang Chien-Hao , Chu Woei Chyn
Published: November 2015

TDP-43 is an RNA-binding protein with multiple function in the regulation of mRNA splicing and translation. However in diseased neuronal cells, TDP-43 forms aggregates and is linked to various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TDP-43 contains an N-terminal domain (NTD), two RNA binding domains (RRM1 and RRM2) and a C-terminal tail region rich in glycine residues. The pathogenic forms of TDP-43 are processed C-terminal fragments containing a truncated RRM2 and a glycine-rich tail. Although extensive studies have focused on this protein, it remains unclear how the dimeric full-length TDP-43 is folded and assembled and how the processed C-terminal fragments are misfolded and aggregated. Here we present the crystal structure of TDP-43 RRM1 domain in complex with a single-stranded DNA. This structure reveals the molecular basis for the recognition of TDP-43 to UG/TG-rich nucleic acids. Combining with SAXS data, we suggest that TDP-43 is assembled into a homodimer via its NTD and interacts with long clusters of UG-rich RNA by its two RRM domains. Moreover, we found that the ALS-linked mutant D169G binds DNA efficiently but is more resistant to thermal denaturation, suggesting that the resistance to degradation is likely linked to TDP-43 proteinopathies. Our data also suggest that the proteolytic cleavage of TDP-43 within RRM2 may remove the NTD dimerization domain and produce unassembled truncated RRM2 fragments with glycine-rich C-terminal tails that can further oligomerize into high-order inclusions.
BswR controls bacterial motility and biofilm formation via modulation RNA rsmZ
Authors: Ye Fuzhou , Wang Chao , Kumar Veerendra , Zhang Lianhui , Gao Yonggui
Published: November 2015

Pseudomonas aeruginosa relies on cell motility and ability to form biofilms to establish infections, however, the mechanism of regulation remains obscure. Here we report that BswR, a XRE (Xenobiotic Response Element) type transcriptional regulator, plays a critical role in regulation of bacterial motility and biofilm formation in P. aeruginosa. Transcriptomic and biochemical analyses showed that BswR counteracts the repressor activity of MvaT, controls the transcription of small RNA rsmZ and regulates the biogenesis of bacterial flagella. The crystal structure of BswR was determined at 2.3 Å resolution; the monomer comprises a DNA-binding domain with a helix-turn-helix (HTH) motif in the N terminus and two helices (6 and 7) with a V-shaped arrangement in the C-terminus. In addition to the contacts between the parallel helices α5 of two monomers, the two helical extensions (6 and 7) intertwine together to form a homodimer, which is the biological function unit. Based on the result of DNase I protection assay together with structural analysis BswR homodimer, we proposed a BswR-DNA model, which suggests a molecular mechanism with which BswR could interact with DNA. Taken together, our results unveiled a novel regulatory mechanism, in which BswR controls the motility and biofilm formation of P. aeruginosa by modulating the transcription of small RNA rsmZ.
O6-carboxymethyl-G forms a sequence context dependent wobble base pair with T
Authors: Zhang Fang , Tsunoda Masaru , Suzuki Kaoru , Kikuchi Yuji , Wilkinson Oliver , Millington Christopher , Margison Geoffrey , Williams David , Takénaka Akio
Published: November 2015

Previously, we reported the crystal structure of DNA d(CGCGXATTCGCG), which revealed that X (O6-carboxymethyl-G) at the 5th position forms a Watson-Crick (WC) type pair with T (Fig. 1a) similar to the canonical A:T pair [1]. In order to investigate the versatility of X in the base-pair formation, another DNA d(CGCXAATTTGCG) containing X at the 4th position has been X-ray analyzed using four different crystals. In the four crystals, the T bases are always largely wobbled into the major groove side to form a hydrogen bond between N3 of T and the carboxyl group of X. In addition, a water molecule bridges between the two bases through two hydrogen bonds to stabilize the pair formation (Fig.1b). This high-wobble (hW) pair is quite different from the previously reported one [1]. Now we succeeded to reveal the two types of pairing modes of X:T pair, WC type and hW type. Since the four crystals were obtained in different conditions, the large displacement of T cannot be ascribed to the interactions with solvent cations. Another possibility is Hoechst33258 used for crystallization. But, as the crystals were obtained in both the presence and the absence of Hoechst33258, this is not the case. The remaining possibility would be the location of the modified base, because the sequence of the used DNA contains an AATT tract at the center and two CGCG tracts at the both ends. The AATT tract is well known to be more flexible (ω*≍ -160) than CGCG tract (ω*≍ -8.70). We found that the WC type X:T pairing requires a large ω angle (-180) between the bases. When X is located at the 5th position (in the AATT tract), the WC type is allowed to occur, while at the 4th position (in the CGCG tract) the WC type is difficult to occur. Here it could be concluded that X form a pair with T in the mode of WC if it is in the flexible tract, while in the mode of hW if it is in the rigid tract, because T base is out of the base stacking. * propeller twist angle between the two bases.
Structural Basis for the Novel Bidirectional Activity of the nanoRNase NrnA
Authors: Schmier Brad , Nelersa Claudiu , Malhotra Arun
Published: November 2015

NanoRNA are RNA molecules 5 nt or less that are generated during several fundamental biological processes, including abortive transcription and RNA turnover. NanoRNA may play a role in the priming of transcription initiation. Degradation of nanoRNA is executed by two distinct families of nanoRNases. In E. coli and higher eukaryotes, Oligoribonuclease, a 3'-5' exoribonuclease from the DEDD family, is responsible for nanoRNA decay. However, orn homologs are missing from the vast majority of bacterial and archaeal genomes, including the Firmicute B. subtilis. NanoRNase A (NrnA), a DHH family phosphodiesterase in B. subtilis, is the founding member of the second class of nanoRNases, and is widespread in organisms lacking orn. NrnA was originally identified as a 3'→5' exonuclease, but we show biochemically that this enzyme is bidirectional, degrading 2-5 nucleotide long RNA oligomers from the 3' end, and longer RNA substrates from the 5' end. We have determined the crystal structure of Bacillus subtilis NrnA, which reveals a dynamic bi-lobal architecture, with the catalytic DHH domain linked to the substrate binding DHHA1 domain via an extended linker. While this arrangement is similar to the structure of RecJ, a 5'→3' DHH family DNase, NrnA has gained an extended substrate-binding patch that is likely responsible for its 3'→5' activity.
Eukaryotic zinc-dependent multifunctional nuclease I
Authors: Kovaľ Tomáš , Lipovová Petra , Podzimek Tomáš , Matoušek Jaroslav , Stránský Jan , Dušková Jarmila , Fejfarová Karla , Skálová Tereza , Hašek Jindřich , Dohnálek Jan
Published: November 2015

Members of eukaryotic nuclease I family are usually zinc, magnesium or calcium dependent, relatively small (about 300 amino acids) glycoproteins with important roles in various apoptotic processes, stress response, DNA repair machinery or sustenance scavenging. They produce 5'-mononucleotides, inorganic phosphate and mononucleosides as end products, have acidic pH optima and are able to cleave different homopolymers with usually no preference for DNA or RNA. P1/S1-like nucleases, a subgroup of nuclease I family, are zinc-dependent, with phospholipase C-like fold. They can be divided to single-strand specific (eg. S1 nuclease from Aspergillus oryzae) or unspecific. TBN1 from Solanum lycopersicum (tomato) is an unspecific P1/S1-like nuclease composed of 277 amino acids with a molecular mass of 37 kDa (when fully glycosylated). TBN1 plays an important role in specific apoptotic functions and cell senescence in plants and also exhibits anticancerogenic properties [1]. For our studies TBN1 was produced recombinantly in Nicotiana benthamiana leafs. Crystals were obtained using a combination of salt and polymer. Datasets for structural analysis were collected at BESSY II (Helmholtz-Zentrum Berlin) [2]. The final model was built and refined using data to 2.15 Å resolution. TBN1 is mainly α-helical with fold stabilized by four disulfide bridges and by the catalytic zinc cluster coordinated at the bottom of the active site cleft. Three oligosaccharides bonded on the surface significantly contribute to solubility of the enzyme. Oligomerization of TBN1 is mediated by binding of a peptide chain to the active site of a neighboring molecule and can be induced by inorganic phosphate. Based on the distribution of surface residues the possible binding sites for nucleic acids with secondary structure were identified. The newly discovered phospholipase activity significantly broadens the substrate promiscuity of TBN1 [3]. This work was supported by the Ministry of Education, Youth and Sports of the Czech Republic (grant No. EE2.3.30.0029), by the project ,,BIOCEV – Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University (CZ.1.05/1.1.00/02.0109), from the European Regional Development Fund, Grant Agency of the Czech Technical University in Prague, grant No. SGS13/219/OHK4/3T/14 and by Institute of Plant Molecular Biology, Biology Centre, AS CR, RVO:60077344.
RNA Biogenesis: Mechanism and Evolution of RNase III
Authors: Ji Xinhua
Published: November 2015

RNase III represents a family of dsRNA-specific endoribonucleases required for RNA maturation and gene regulation. Bacterial RNase III and eukaryotic Rnt1p, Drosha, and Dicer are representative members of the family. The bacterial enzyme possesses a single RNase III domain (RIIID) followed by a dsRNA-binding domain (dsRBD); Rnt1p is defined by the presence of an N-terminal domain (NTD), a RIIID, and a dsRBD; Drosha contains N-terminal P-rich and RS-rich domains followed by two RIIIDs and a dsRBD; and Dicer possesses N-terminal helicase, DUF283, and PAZ domains followed by two RIIIDs and a dsRBD. It is the N-terminal extension beyond the RIIID that distinguishes eukaryotic RNase IIIs from the bacterial enzyme. My lab has been studying the structure and mechanism of RNase III enzymes since 1996. We have reported a total of eleven crystal structures of bacterial RNase III in complex with dsRNA at various catalytic stages of the enzyme, including the first structure of a catalytically meaningful RNase III-RNA complex (Gan et al., Cell, 124:355-366, 2006), and thereby well characterized the mechanism of action for the bacterial enzyme (Court et al., Annu Rev Genet, 47:405-431, 2013). We have also determined the crystal structure of yeast Rnt1p post-cleavage complex, the first structure of a eukaryotic RNase III complexed with RNA in a catalytically meaningful manner (Liang et al., Molecular Cell, 54:431-444, 2014, featured article on the issue cover). Strikingly, the NTD and dsRBD of Rnt1p function as two rulers for substrate selection. This unusual mechanism represents an example of the evolution of substrate selectivity and provides a framework for understanding the catalytic mechanism of eukaryotic RNase IIIs, including Drosha and Dicer.
Preliminary crystallographic analysis of SETMAR bound to DNA
Authors: Chen Qiujia , Lee Suk-Hee , Georgiadis Millie
Published: November 2015

SETMAR, a recently identified double strand break (DSB) repair enzyme in the human genome, contains an N-terminal SET domain and a C-terminal MAR domain. This chimeric protein arose through the fusion of a mariner-family DNA transposase gene, Hsmar1, downstream of a SET histone methyltransferase gene approximately 50 million years ago [1]. Although the SETMAR transposase domain retains the ability to bind terminal inverted repeat (TIR) DNA sequence, which is the hallmark of DNA transposons, it is no longer a functional transposase [2]. Nonetheless, the transposase domain with only 19 amino acid substitutions as compared to the ancestral Hsmar1 transposase has been under a strong selective evolutionary pressure suggesting that the transposase domain is functionally important. Determining how SETMAR interacts with DNA is central to understanding the molecular basis of its evolved DNA repair activity. Toward this goal, we have focused initially on the interaction of the DNA-binding domain (DBD) of the SETMAR transposase domain with TIR DNA. The DBD of SETMAR has been overexpressed and purified. A complex formed between SETMAR DBD and its transposon TIR DNA has been crystallized by using the hanging-drop vapor diffusion method. The crystals diffract to 3.15 Å resolution and exhibit orthorhombic symmetry (C2221), with unit-cell dimensions of a=72.233 Å, b=164.385 Å, and c=67.957 Å. As there is no suitable search model available, we are currently pursuing experimental phasing approaches in order to solve this structure. We anticipate the structural analysis of DBD of SETMAR bound to transposon DNA will provide insight into the mechanism by which SETMAR recognizes both TIR and non-TIR DNA.
Structural basis for inhibition of complement C5a by an L-RNA aptamer
Authors: Yatime Laure , Maasch Christian , Hoehlig Kai , Klussmann Sven , Vater Axel , Andersen Gregers
Published: November 2015

Complement is a central component of innate immunity providing a first line of defense against invading pathogens. It also bridges the innate and adaptive immunity, initiates the inflammatory response, and participates in immune surveillance. The anaphylatoxin C5a, generated during complement activation, is a potent inflammatory mediator which induces chemotaxis, oxidative burst, histamine release and increased vasodilatation, through G-protein coupled receptor signaling. Although inflammation is an integral part of the healing process following tissue damage and infection, excessive levels of C5a correlate with the onset of various inflammatory disorders including sepsis, rheumatoid arthritis, acute lung injury, ischemia-reperfusion injury, allergy, transplantation and asthma. Therapeutical targeting of the C5a:receptor axis is considered a promising strategy to down-regulate complement-mediated inflammation. The L-aptamer NOX-D20, fully composed of non-natural mirror-image nucleotides (a so called Spiegelmer), has been identified as a potent C5a inhibitor. NOX-D20 has already shown encouraging efficacy in an experimental model of sepsis [1]. Here, we present the first crystallographic structure of an active Spiegelmer®, NOX-D20, bound to its physiological target, the mouse C5a anaphylatoxin, determined at 1.8 Å resolution. The structure reveals a complex 3D-architecture for the L-RNA molecule that wraps around C5a, including an intramolecular G-quadruplex stabilized by a Ca2+ ion as validated through anomalous diffraction data. The aptamer:C5a binding mode observed in the structure was validated through mutational studies using SPR. Our structure provides a molecular basis for NOX-D20 inhibitory properties and allows us to rationalize NOX-D20 selectivity towards human and mouse C5a
Structural basis for processive DNA synthesis by yeast DNA polymerase ε
Authors: Hogg Matthew , Osterman Pia , Bylund Göran , Ganai Rais , Lundström Else-Britt , Sauer-Eriksson Elisabeth , Johansson Erik
Published: November 2015

DNA polymerase ε (Pol ε) is a high-fidelity polymerase that participates in leading-strand synthesis during eukaryotic DNA replication in eukaryotic cells. The 2.2 Å ternary structure of the 142 kDa catalytic core of Pol ε from Saccharomyces cerevisiae in complex with DNA and an incoming nucleotide has recently been determined [1]. The structure provides information about the selection of the correct nucleotide and the positions of amino acids that might be critical for proofreading activity. Pol ε has the highest fidelity among B-family polymerases despite the absence of an extended β-hairpin loop that is required for high-fidelity replication by other B-family polymerases. Moreover, the catalytic core has a new domain (i.e. the P-domain) that allows Pol ε to encircle the nascent double-stranded DNA and enhance processifivity of the polymerase. The structure provides valuable insights into the similarities and differences between Pol ε and other B-family polymerases, and suggests possible mechanisms responsible for the high processivity and fidelity of Pol ε.
Probing protein - DNA interaction by single molecule and structural analysis
Authors: Jin Jianshi , Lian Tengfei , Gu Chan , Gao Yiqin , Sun Yujie , Xie X. Sunney , Su Xiao-Dong
Published: November 2015

In proteins, conformational change impacting their function has been well investigated in the past decades, and was named `allosteric effect'. However, in DNA-protein interaction, the concept of DNA conformational change caused by DNA-protein binding will affect another nearby DNA-binding protein has not been well investigated and understood. Combined with structural biology and Single Molecule Assays, we can now probe and study allosteric propagation through DNA which exists as a fundamental property in DNA-protein interaction, and this allosteric effect through DNA can fine tune gene expression. Therefore, DNA conformational changes should be seriously considered and analyzed for DNA –protein interactions in general.
Electronic transport properties of graphene nanostructures
Authors: Wakabayashi Katsunori
Published: November 2015

The electronic states of graphene near the Fermi energy are well described by massless Dirac Fermion. The presence of edges, however, makes strong implications for the spectrum of the electrons. In graphene nanoribbons with zigzag edges, localized states appear at the edge with energies close to the Fermi level. In contrast, edge states are absent for ribbons with armchair edges. In my talk, we focus on edge and nanoscale effect on the electronic properties of graphene nanoribbons. We discuss the following aspects of graphene nanostructured systems. (1) In zigzag nanoribbons, for nonmagnetic long-ranged disorder, a single perfectly conducting channel emerges associated with a chiral mode due to the edge state, i.e., the absence of the localization in this class. (2) We show the electronic transport properties of graphene nanojunctions crucially depend on the peripheral lattice structures. The condition for electron confinement is discussed. (3) We will discuss the effect of edge chemical modification on magnetic properties of nanographene systems. Also, we discuss the hole doping effect on the spin-polarized states appearing along the graphene zigzag edges. Our studies reveal that the peculiar electronic, magnetic and transport properties of graphene nanostructured systems. In addition, we present our recent work on graphene double layer structure (GDLS), where two graphene layers are separated by a thin dielectric. We will discuss the dielectric environment effect on the charged-impurity-limited carrier mobility of the GDLS on the basis of the Boltzmann transport theory. It is found that carrier mobility strongly depends on the dielectric constant of the barrier layer if the interlayer distance becomes larger than the inverse of the Fermi wave vector. Our results suggest effective use of ultra-thin dielectric barriers and a practical design strategy to improve the charged-impurity-limited mobility of the GDLS.
Tailoring electronic properties of 2D crystals by strain engineering
Authors: Pereira Vitor
Published: November 2015

One of the enticing features common to most of the two-dimensional electronic systems that, in the wake of (and in parallel with) graphene, are currently at the forefront of materials science research is the ability to easily introduce a combination of planar deformations and bending in the system. Since the electronic properties are ultimately determined by the details of atomic orbital overlap, such mechanical manipulations translate into modified (or, at least, perturbed) electronic properties. Graphene, in particular, on account of its exceptional range of elastic deformation, complemented by an unusual electron-phonon coupling that can be captured by the concept of a fictitious or pseudo-magnetic field (PMF), has taught us that its intrinsic electronic properties can be molded by many more, and much richer, approaches that can be applied to 3D bulk solids. The ability to manipulate the local strain distribution in graphene opens the enticing prospect of strain-engineering its electronic and optical properties, as well as of enhancing interaction and correlation effects. I will describe some examples of how strain-engineered graphene can have richer spectral, transport, and optical properties, or how it allows potentially novel device functionalities and tunability. Some concepts will be discussed in parallel with a summary of selected experimental work. A general optimization framework for tailoring physical properties of 2D crystals by manipulating the state of local strain, and allowing a one-step route from their design to experimental implementation, will be presented, together with a discussion of examples of its application in the design of nanoscale transport devices.
Powder diffraction and DFT studies of synthetic insect pheromones
Authors: Fitch Andrew , Brooks Lee , Pattison Philip , Brunelli Michela , Jones Graeme
Published: November 2015

Eight chiral monomethyl alkanes have been synthesized and their crystal structures solved from high resolution powder diffraction patterns collected using synchrotron radiation. Such compounds have been seen to act as recognition pheromones in social insects. Carbon chain lengths varied from C25to C31with the methyl group at various positions along the chain. One compound, (S)-7-methylnonacosane, also formed a low quality single crystal from which its structure was solved and refined. Although the powder diffraction patterns were good enough to solve the crystal structures, using the standard technique of real-space simulated annealing, with near-linear molecules, chemically unreasonable distortions occurred during Rietveld refinement unless many distance, angle and torsion restraints were imposed. From the results of the single-crystal structure it is evident that there is a gentle bend in the molecule close to the position of the methyl side chain. Thus imposing a near-linear molecule is incorrect, and giving sufficient freedom in the Rietveld refinement to allow the molecule to bend leads to an inaccurate structure. In short, the correct structure must be known to judge the strength of the restraints to apply, and this must vary at different parts of the chain. As an alternative to refining the structure from the powder diffraction data, the structures have been optimized via dispersion-corrected DFT calculations (Van der Streek and Neumann, 2010) starting from the powder structures. Agreement between the single-crystal and DFT-minimized structures is satisfactory, with an rms distance of 0.054 Å and a maximum distance of 0.132 Å when comparing carbon atoms positions. With this approach, a well defined structure optimization strategy is used for all the crystal structures. The molecules studied fall into two packing types, (both with monoclinic symmetry), depending on the position of the methyl group on the main carbon chain relative to the overall chain length.
Combinatorial Approach for solving complex structures from low resolution data
Authors: Gourdon Olivier
Published: November 2015

Crystal structure solution from diffraction experiments is an essential step in materials science, chemistry, physics and geology. Unfortunately, numerous factors render this process in some cases quite complex. Experimental conditions, such as high pressure or poor crystallinity, often complicate characterization. Furthermore, many applied materials such as batteries and/or energy storage materials, contain light elements such as Li and H that only weakly scatter X-rays. In that case a combined X-ray /neutron analysis is required. Moreover, the quality of charge-discharge cycling of these materials is at the cost of the crystallinity which brings more complexity to have a good level of understanding of the cycling process. Similar issues could also be raised for the analysis of some minerals which possess numerous phases which could be eventually amorphous. Finally, structural refinements generally require significant human input and intuition, as they rely on good initial guesses for the target structure. To eliminate part of these guesses, we are supporting a more combinatorial approach which uses X-ray and Neutron scattering experiments but also theoretical tools such as DFT and/or Molecular dynamics calculations as well as data mining tools. This presentation will mainly focus on recent experiments performed on two different high intensity/medium resolution T-o-F neutron diffractometers at LANSCE: HIPPO (High Pressure Preferred Orientation) and HIPD (High Intensity Powder Diffractometer). Examples will be used to highlight the level of information which can be achieved using these combined strategies and how we can connect it to the physical properties.
Lower resolution Laue neutron data yield correct nanocluster formulations
Authors: Edwards Alison
Published: November 2015

"The renaissance in Laue studies - at neutron sources - provides us with access to single crystal neutron diffraction data for synthetic compounds without requiring synthesis of prohibitively large amounts of compound or improbably large crystals. Such neutron diffraction studies provide vital data where proof of the presence or absence of hydrogen in particular locations is required and which cannot validly be proved by X-ray studies. Since the commissioning of KOALA at OPAL in 2009[1] we have obtained numerous data sets which demonstrate the vital importance of measuring data even where the extent of the diffraction pattern is at relatively low resolution - especially when compared to that obtainable for the same compound with X-rays. In the Laue experiment performed with a fixed radius detector, data reduction is only feasible for crystals in the ""goldilocks"" zone – where the unit cell is relatively large for the detector, a correspondingly low resolution diffraction pattern in which adjacent spots are less affected by overlap will yield more data against which a structure can be refined than a pattern of higher resolution – one where neighbouring spots overlap rendering both unusable (in our current methodology). Analogous application of powder neutron diffraction in such determinations is also considered. Single crystal neutron diffraction studies of several important compounds (up to 5KDa see figure below)[2] in which precise determination of hydride content by neutron diffraction was pivotal to the final formulation will be presented. The neutron data sets typically possess 20% or fewer unique data at substantially "lower resolution" than the corresponding X-ray data sets. Careful refinement clearly reveals chemical detail which is typically unexplored in related X-ray diffraction studies reporting high profile chemistry despite the synthetic route being one which hydride ought to be considered/excluded in product formulation."
Common Packing Motif in Salts of H-Acid, and the Incommensurate Sodium Hydrate
Authors: Rowsell Jesse , Rackauckas Christopher , Kang Justin , Rosenberger James , Zeller Matthias
Published: November 2015

"""H-Acid"" (4-ammonio-5-hydroxynaphthalene-2,7-disulfonate) is a coal tar derivative and important intermediate in the manufacture of hundreds of dyes. Despite the fact that on the order of one million metric tons of the sodium salt have been manufactured in the past century, no crystal structures incorporating this organosulfonate have been reported. Diffraction quality needles of the hydrated sodium salt are prepared by slow cooling a concentrated aqueous solution under anaerobic conditions. Variable temperature X-ray diffraction studies revealed the structure exhibits positional disorder of donor atoms around aqua-bridged Na+ dimers between room temperature and 180 K. Upon further cooling the structure undergoes a reversible phase transition to an ordered, incommensurately modulated structure with retention of crystal quality. Structure elucidation of over a dozen other salts of H-Acid revealed in all cases the adoption of a stacking motif reinforced by hydrogen bonds involving a ""keystone"" water molecule. This water molecule is also retained during in situ dehydration of the sodium salt at elevated temperature; surprisingly, a sodium-coordinated water molecule is the first to be released."
Anisotropic strain and Jahn-Teller effect of chiral complexes and metal oxides
Authors: Orii Yuta , Kobayashi Masaki , Nagai Yuki , Atsumi Kohei , Tazaki Daichi , Ehara Satoshi , Akitsu Takashiro
Published: November 2015

For about a decade, we have systematically investigated thermally-accessible lattice strain and local pseudo Jahn-Teller distortion of [CuL2]3[M(CN)6]2·4H2O (L = (1R, 2R)-cyclohexanediamine; M = Cr, Co, and Fe). In mononuclear Cu(II) complexes, (pseudo) Jahn-Teller effect plays an important role in flexible distortion of crystal structures especially Cu(II) coordination environment. Beside Jahn-Teller distortion, we have dealt with some factors for example, metal substitution as bimetallic assemblies, chirality of ligands, and H/D isotope effect to vary intermolecular interaction and crystal packing. According to the course work using variable temperature PXRD, we have found that anisotropy of crystal strain distortion did not corporate with Jahn-Teller distortion around local coordination environment because of the discrepancy of the crystallographic axes and molecular alignment. In order to elucidate the anisotropic control of lattice strain and Jahn-Teller distortion closely, we have employed transition metal oxide with orthogonal or layered structures to prepare composite materials with the chiral metal complexes for discussion of thermally-accessible PXRD changes and IR shift due to adsorption. At first, we have employed chiral one-dimensional zig-zag Cu-Cr bimetallic assemblies and their oxides prepared by burining. Based on variable temperature XRD patterns, a linear correlation (lnK = a/T + b) of K (=d(T)-d(0)/d(T)) values, where d(T) and d(0) are spacing of lattice plane (d = nλ/(2sinθ)) at T K and 0 K (extrapolated), respectively, and its deviation from ideal correlation indicates degree of anisotropic lattice distortion of the composite materials. For example, we could observe LiMnO2, typical material of lithium ion battery, was enhanced anisotropic lattice strain along the b axis or the (011) plane added by [CuL2(H2O)2](NO3)2 complexes. Which may prevent from breaking down regular crystal structures during charge-discharge of secondary battery.
Visualizing Structural Modulation in Melilite Electrolytes by X-ray and Electron
Authors: Cong Hengjiang , Zhang Huaijin
Published: November 2015

Nowadays novel melilite-type oxides are of growing interest as promising new oxide-ion conductors with potential use in clean energy devices such as solid oxide fuel cells (SOFCs).[1] These oxides have a general formula of A2BC2O7, where A = large divalent alkali earth metals like Ca, Sr, Ba or trivalent rare earth metals like La, Nd, Gd; B and C = small cations like Mg, Si, Ga. In addition to the conventional tetragonal symmetry with space group P¯421m, these melilites also show a five-dimensional superspace symmetry P¯421m(α, α, 0)00s(¯α, α, 0)000 with modulation vectors q1=α(a*+b*) and q2=α(-a*+b*). Both displacive (cation and anion) and occupational (cation) modulations have been found.[2-3] Here a series of melilite single crystals, such as Ca2MgSi2O7, SrLaGa3O7, SrGdGa3O7, BaLaGa3O7 and CaNdGa3O7 have been successfully obtained using the optical floating zone and Czochralski method. Further investigations were made by a combination of temperature-variant X-ray diffraction and electron microscopy. The mechanism between substitutions in A- and B- sites and structural modulations in melilites is clarified, which paves the way for future crystallographic optimization of electrolyte performances via tailoring interstitial oxygen concentration and enhancing ion mobility.