bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNAs templating chromatin structure for dosage compensation in animals
Authors: Wutz Anton 
Published: April 2003

AbstractThe role of RNA as a messenger in the expression of the genome has been long appreciated, but its functions in regulating chromatin and chromosome structure are no less interesting. Recent results have shown that small RNAs guide chromatin‐modifying complexes to chromosomal regions in a sequence‐specific manner to elicit transcriptional repression. However, sequence‐specific targeting by means of base pairing seems to be only one mechanism by which RNA is employed for epigenetic regulation. The focus of this review is on large RNAs that act in the dosage‐compensation pathways of flies and mammals. These RNAs associate with chromatin over the length of whole chromosomes and are crucial for spreading epigenetic changes in chromatin structure. They do not appear to act in a sequence‐specific manner but might provide scaffolds for co‐operative binding of chromatin‐associated complexes that enable spreading of chromatin modifications. BioEssays 25:434–442, 2003. © 2003 Wiley Periodicals, Inc.
NAADP on the up in pancreatic beta cells—a sweet message?
Authors: Patel Sandip 
Published: April 2003

AbstractPancreatic beta cells secrete insulin in response to elevated plasma glucose levels in a Ca2+‐dependent fashion. Released insulin may act on the beta cell itself to promote further insulin synthesis and release. Recent studies by Johnson and Misler,1 Masgrau et al.2 and Mitchell et al.3 provide strong evidence (1) for the existence of intracellular Ca2+ stores sensitive to NAADP, a potent Ca2+‐mobilizing messenger, and (2) that these Ca2+ stores are involved in both glucose‐ and insulin‐mediated signal transduction. NAADP may therefore play an important role in controling secretion of insulin from pancreatic beta cells. BioEssays 25:430–433, 2003. © 2003 Wiley Periodicals, Inc.
Playing by pair‐rules?
Authors: Davis Gregory K. , Patel Nipam H. 
Published: April 2003

AbstractAlthough in Drosophila pair‐rule genes play crucial roles in the genetic hierarchy that subdivides the embryo into segments, the extent to which pair‐rule patterning is utilized by different arthropods and other segmented phyla is unknown. Recent data of Dearden et al.1 and Henry et al.,2 however, hint that a pair‐rule mechanism might play a role in the segmentation process of basal arthropods and vertebrates. BioEssays 25:425–429, 2003. © 2003 Wiley Periodicals, Inc.
Idiomatic (gene) expressions
Authors: Rockman Matthew V. 
Published: April 2003

AbstractHidden among the myriad nucleotide variants that constitute each species' gene pool are a few variants that contribute to phenotypic variation. Many of these differences that make a difference are non‐coding cis‐regulatory variants, which, unlike coding variants, can only be identified through laborious experimental analysis. Recently, Cowles et al.1 described a screening method that does an end‐run around this problem by searching for genes whose cis regulation varies without having to find the polymorphic nucleotides that influence transcription. While we will continue to require a diverse arsenal of experimental methods, this versatile method will speed the identification of functional genetic variation. BioEssays 25:421–424, 2003. © 2003 Wiley Periodicals, Inc.
The digital origin of human language—a synthesis
Authors: Noll Hans 
Published: April 2003

AbstractThe fact that all languages known are digital poses the question of their origin. The answer developed here treats language as the interface of information theory and molecular development by showing previously unrecognized isomorphisms between the analog and digital features of language and life at the molecular level. Human language is a special case of signal transduction and hence is subject to the coding aspects of Shannon's theorems and the analog aspects of pattern recognition, each represented by genotype and phenotype. Digital language acquisition is late in evolution and postnatal development and requires a neural reorganization by a mechanism of somatic network programming in response to the environment. Such a mechanism would solve the Chomsky conundrum of how children can learn any language without knowing rules of grammar too numerous to be encoded genotypically. BioEssays 25:489–500, 2003. © 2003 Wiley Periodicals, Inc.
Conformational behavior of chondroitin and chondroitin sulfate in relation to their physical properties as inferred by molecular modeling
Authors: Rodríguez‐Carvajal Miguel A. , Imberty Anne , Pérez Serge 
Published: April 2003

AbstractChondroitin and chondroitin sulfates belong to the family of glycosaminoglycans. They are most widely distributed in animal tissues, where they are involved in structural functions and in cell–cell communication. Their basic structures consist of a disaccharidic repeating unit of β‐D‐glucuronic acid (GlcA) and 2‐acetamido‐2‐deoxy‐β‐D‐galactose (GalNAc), this latter being sulfated at different positions. Molecular mechanics has been applied to calculate the adiabatic energy maps for each of the constituting disaccharides of chondroitin, chondroitin 4‐sulfate, and chondroitin 6‐sulfate using the MM3 force field. Based on these maps, higher levels of structural organization have been simulated. On one hand, the disordered state is studied through a Metropolis‐based algorithm; the resulting chains present a behavior of semirigid polymers, with an order of stiffness: chondroitin 4‐sulfate > chondroitin > chondroitin 6‐sulfate. On the other hand, the exploration of the stable ordered forms leads to numerous helical conformations of comparable energies. Several of these conformations correspond to the experimentally observed ones. The ability of coordination with cations has also been explored, resulting in a preferential stereospecificity for calcium ions when compared to sodium ions. © 2003 Wiley Periodicals, Inc. Biopolymers 69:15–28, 2003
Conformational preferences of the amylin nucleation site in SDS micelles: An NMR study
Authors: Mascioni Alessandro , Porcelli Fernando , Ilangovan Udayar , Ramamoorthy Ayyalusamy , Veglia Gianluigi 
Published: April 2003

AbstractHuman islet amyloid polypeptide (hIAPP), or amylin, is a 37 amino acid hormone secreted by pancreatic β‐cells. hIAPP constitutes ∼90% of the amyloid deposits found in type II diabetic patients. It has been shown that the central region of the peptide (hIAPP20–29) constitutes the nucleation site for the amyloidogenic process with F23 playing a key role in the formation of the β‐pleated structures. In addition, it has been proposed that an important stage in the cytotoxicity of hIAPP is its interaction with the β‐cell membranes. As a first step toward the characterization of the interaction of hIAPP with cell membranes, we determined conformational preferences of hIAPP20–29in membrane‐mimicking environments. We found that upon interacting with negatively charged micelles, the dominant conformation of hIAPP20–29is a distorted type I β‐turn centered on residues F23 and G24, with F23, A25, and I26 forming a small hydrophobic cluster that may facilitate the interaction of this peptide with the membrane bilayer. Moreover, we were able to elucidate the topological orientation of the peptide that is absorbed on the micelle surface, with the hydrophobic cluster oriented toward the hydrocarbon region of the micelles and both N‐ and C‐termini exposed to the solvent. © 2003 Wiley Periodicals, Inc. Biopolymers 69: 29–41, 2003
Free energy of proton binding in proteins
Authors: Poland Douglas 
Published: April 2003

AbstractIn this article we use literature data on the titration of denatured ribonuclease to test the accuracy of proton‐binding distributions obtained using our recent approach employing moments. We find that using only the local slope of the titration curve at a small number of points (five, for example) we can reproduce the detailed proton‐binding distribution at all pH values. Our method gives the complete proton‐binding polynomial for a given protein and each coefficient in this polynomial in turn yields the free energy for binding a given number of protons in all ways to the protein. Using these net free energies, we can then compute the average proton‐binding free energy per proton as a function of the fraction of protons bound. We find that this function is remarkably similar for different proteins, even for proteins that exhibit quite different titration behavior. For the special case of binding to independent sites, we obtain simple relations for the first and last terms in the free energy per‐proton function. For this special case we also can calculate the distribution functions giving the probability that a molecule has a given number of positive or negative charges and the joint distribution that a molecule simultaneously has a given number of positive and negative charge. © 2003 Wiley Periodicals, Inc. Biopolymers 69: 60–71, 2003
Surprising roles of electrostatic interactions in DNA–ligand complexes
Authors: Howerton Shelley B. , Nagpal Akankasha , Dean Williams Loren 
Published: April 2003

AbstractThe positions of cations in x‐ray structures are modulated by sequence, conformation, and ligand interactions. The goal here is to use x‐ray diffraction to help resolve structural and thermodynamic roles of specifically localized cations in DNA–anthracycline complexes. We describe a 1.34 A˚ resolution structure of a CGATCG2–adriamycin2 complex obtained from crystals grown in the presence of thallium (I) ions. Tl+ can substitute for biological monovalent cations, but is readily detected by distinctive x‐ray scattering, obviating analysis of subtle differences in coordination geometry and x‐ray scattering of water, sodium, potassium, and ammonium. Six localized Tl+ sites are observable adjacent to each CGATCG2–adriamycin2 complex. Each of these localized monovalent cations are found within the G‐tract major groove of the intercalated DNA–drug complex. Adriamycin appears to be designed by nature to interact favorably with the electrostatic landscape of DNA, and to conserve the distribution of localized cationic charge. Localized inorganic cations in the major groove are conserved upon binding of adriamycin. In the minor groove, inorganic cations are substituted by a cationic functional group of adriamycin. This partitioning of cationic charge by adriamycin into the major groove of CG base pairs and the minor groove of AT base pairs may be a general feature of sequence‐specific DNA–small molecule interactions and a potentially useful important factor in ligand design. © 2003 Wiley Periodicals, Inc. Biopolymers 69: 87–99, 2003
Binding of Europium(III) ions to RNA stem loops: Role of the primary hydration sphere in complex formation
Authors: Mundoma Claudius , Greenbaum Nancy L. 
Published: April 2003

AbstractUnderstanding the process by which RNA molecules fold into stable structures includes study of the role of site‐bound metal ions. Because the alkaline earth metal ions typically associated with RNA structure [most often Mg(II)] do not provide convenient spectroscopic signals, replacement with metal ions having spectroscopically useful properties has been a valuable approach. The luminescence properties of the lanthanide(III) series, in particular europium(III), have made them useful in the study of complexation with biomolecules. We review the physical, chemical, and spectroscopic characteristics of Eu(III) that contribute to its value as a probe of RNA–metal ion interactions, and examples of information obtained from studies of Eu(III) bound to small RNA stem loops. Although Eu(III) has similar site preference to Mg(II), luminescence and isothermal titration calorimetry measurements indicate that Ln(III) loses water molecules from the inner hydration sphere more readily than does Mg(II), resulting in more direct coordination between RNA and the metal ion and very different energetics of binding. In some cases, e.g., a GAAA tetraloop, binding appears to occur by a lock and key process; in the same base sequence containing certain deoxynucleoside substitutions that alter loop structure, binding appears to occur by an induced fit process. © 2003 Wiley Periodicals, Inc. Biopolymers 69:100–109, 2003
Reflections on apparent DNA bending by charge variants of bZIP proteins
Authors: Hardwidge Philip R. , Parkhurst Kay M. , Parkhurst Lawrence J. , Maher L. James 
Published: April 2003

AbstractBasic‐leucine zipper (bZIP) proteins have been studied intensely as transcription factors. It has been proposed that the bZIP domain might modulate transcription activation through the induction of conformational changes in the DNA binding site. We have been interested in using bZIP peptides as convenient models with which to study the role of asymmetric phosphate neutralization in DNA bending. DNA bending experiments have yielded discordant results for bZIP peptides studied by electrophoretic‐ vs solution‐based assays. We review the history of DNA bending assays involving bZIP peptides and introduce the reader to examples of discordant results. Our recent published experiments designed to clarify this field of study will then be reviewed. The engineering of protein fusions has established that electrophoretic phasing assays are relatively insensitive to precise protein structure/conformation and instead appear to report DNA bending, as influenced by protein charge. New applications of time‐resolved fluorescence resonance energy transfer (FRET) have allowed for the first time corroboration of electrophoretic phasing assays with solution‐based FRET measurements. We report that two conventional DNA bending assays that rely on DNA ligation cannot be applied to analysis of the bZIP peptides we studied due to ligation inhibition. © 2003 Wiley Periodicals, Inc. Biopolymers 69: 110–117, 2003
The solution structures and activity of caerin 1.1 and caerin 1.4 in aqueous trifluoroethanol and dodecylphosphocholine micelles
Authors: Wegener Kate L. , Carver John A. , Bowie John H. 
Published: April 2003

AbstractThe caerin 1 peptides are among the most powerful of the broad‐spectrum antibiotic amphibian peptides. Caerin 1.1 has previously been shown to form an amphipathic helix–bend–helix structure in aqueous trifluoroethanol (H. Wong, J. H. Bowie, and J. A. Carver European Journal Biochemistry, 1997, Vol. 247, pp. 545–557) and structure–activity relationship studies indicate that both helices are required for activity, as well as flexibility in the bend region connecting the two. The structure of caerin 1.1 in dodecylphosphocholine micelles was investigated and shown to be very similar to that determined in aqueous trifluoroethanol. Caerin 1.4, which is identical to caerin 1.1, but with serine residues replacing Val5 and Gly7, is less active than caerin 1.1 against most bacterial species but has improved activity against Escherichia coli and Micrococcus luteus. The solution NMR structure of caerin 1.4 was determined in both aqueous trifluoroethanol and dodecylphosphocholine micelles, and was shown to be similar to caerin 1.1. It was concluded that differences in the hydrophobicity and hydrophilic angle of the first helix are probably responsible for the different spectra of antibacterial activity. The similarity of the structures calculated in aqueous trifluoroethanol and dodecylphosphocholine micelles suggests that, for caerin 1.1 and 1.4, these solvent systems are equally as good at representing a membrane environment. © 2003 Wiley Periodicals, Inc. Biopolymers 69: 42–59, 2003
The Ac–RGD–NH2 peptide as a probe of slow conformational exchange of short linear peptides in DMSO
Authors: Biris Nikolaos , Stavrakoudis Athanassios , Politou Anastasia S. , Mikros Emmanuel , Sakarellos‐Daitsiotis Maria , Sakarellos Constantinos , Tsikaris Vassilios 
Published: April 2003

AbstractAccording to general belief, the conformational information on short linear peptides in solution derived at ambient temperature from NMR spectrometry represents a population‐weighted average over all members of an ensemble of rapidly interconverting conformations. Usually the search for discrete conformations is concentrated at low temperatures especially when sharp NMR resonances are detected at room temperature. Using the peptide Ac–RGD–NH2 (Ac–Arg–Gly–Asp–NH2, Ac: acetyl) as a model system and following a new approach, we have been able to demonstrate that short linear peptides can adopt discrete conformational states in DMSO‐d6 (DMSO: dimethylsulfoxide) which vary in a way critically dependent on the reconstitution conditions used before their dissolution in DMSO‐d6. The conformers are stabilized by intramolecular hydrogen bonds, which persist at high temperatures and undergo a very slow exchange with their extended structures in the NMR chemical shift time scale. The reported findings provide clear evidence for the occurrence of solvent‐induced conformational exchange and point to DMSO as a valuable medium for folding studies of short linear peptides. © 2003 Wiley Periodicals, Inc. Biopolymers 69:72–86, 2003
Modeling the dynamics of the solvated SL1 domain of HIV‐1 genomic RNA
Authors: La Penna G. , Genest D. , Perico A. 
Published: April 2003

AbstractA mode‐coupling solution of the Smoluchowski diffusion equation (MCD theory), designed to describe the dynamics of wobbling macromolecules in water, is applied to a macromolecular bead model including water beads in the nearest layers. The necessary statistical averages are evaluated by time averaging along a molecular dynamics (MD) trajectory where both solute and water are introduced as atomistic models. The cross peaks in 1H nuclear Overhauser effect spectroscopy (NOESY) NMR spectra that are routinely measured to determine biological structures are here calculated for the mutated 23 nucleotides stem‐loop fragment of the SL1 domain in the HIV‐1Lai genomic RNA. The calculations are in acceptable agreement with experiments without requiring any screening of the hydrodynamic interactions. The screening of hydrodynamics was necessary in previous MCD calculations obtained by using the same full atomistic MD trajectory, but a nonsolvated frictional model. © 2003 Wiley Periodicals, Inc. Biopolymers 69: 1–14, 2003
A thermodynamic framework for the magnesium‐dependent folding of RNA
Authors: Misra Vinod K. , Shiman Ross , Draper David E. 
Published: April 2003

AbstractThe goal of this review is to present a unified picture of the relationship between ion binding and RNA folding based on recent theoretical and computational advances. In particular, we present a model describing how the association of magnesium ions is coupled to the tertiary structure folding of several well‐characterized RNA molecules. This model is developed in terms of the nonlinear Poisson–Boltzmann (NLPB) equation, which provides a rigorous electrostatic description of the interaction between Mg2+ and specific RNA structures. In our description, most of the ions surrounding an RNA behave as a thermally fluctuating ensemble distributed according to a Boltzmann weighted average of the mean electrostatic potential around the RNA. In some cases, however, individual ions near the RNA may shed some of their surrounding waters to optimize their Coulombic interactions with the negatively charged ligands on the RNA. These chelated ions are energetically distinct from the surrounding ensemble and must be treated explicitly. This model is used to explore several different RNA systems that interact differently with Mg2+. In each case, the NLPB equation accurately describes the stoichiometric and energetic linkage between Mg2+ binding and RNA folding without requiring any fitted parameters in the calculation. Based on this model, we present a physical description of how Mg2+ binds and stabilizes specific RNA structures to promote the folding reaction. © 2003 Wiley Periodicals, Inc. Biopolymers 69: 118–136, 2003
Comments on selected aspects of nucleic acid electrostatics
Authors: Manning Gerald S. 
Published: April 2003

AbstractRecent experimental, theoretical, and computational developments in the field of nucleic acid electrostatics have brought interesting concepts to the fore. The phosphate charge on the double helix apparently influences its structure. When the charge is neutralized asymmetrically, the resulting force imbalance drives bending toward the neutralized side. When the charge is uniformly neutralized, the force imbalance acts to buckle the helical axis, resulting in a compact tertiary conformation. Sharing of condensed counterions by single strands is a stabilizing factor for formation of the double helix. Sharing of condensed counterions by two double helices causes clustering of DNA and may be a factor in RNA folding. Support for these statements is reviewed. © 2003 Wiley Periodicals, Inc. Biopolymers 69: 137–143, 2003
A unified model for the origin of DNA sequence‐directed curvature
Authors: Hud Nicholas V. , Plavec Janez 
Published: April 2003

AbstractThe fine structure of the DNA double helix and a number of its physical properties depend upon nucleotide sequence. This includes minor groove width, the propensity to undergo the B‐form to A‐form transition, sequence‐directed curvature, and cation localization. Despite the multitude of studies conducted on DNA, it is still difficult to appreciate how these fundamental properties are linked to each other at the level of nucleotide sequence. We demonstrate that several sequence‐dependent properties of DNA can be attributed, at least in part, to the sequence‐specific localization of cations in the major and minor grooves. We also show that effects of cation localization on DNA structure are easier to understand if we divide all DNA sequences into three principal groups: A‐tracts, G‐tracts, and generic DNA. The A‐tract group of sequences has a peculiar helical structure (i.e., B*‐form) with an unusually narrow minor groove and high base‐pair propeller twist. Both experimental and theoretical studies have provided evidence that the B*‐form helical structure of A‐tracts requires cations to be localized in the minor groove. G‐tracts, on the other hand, have a propensity to undergo the B‐form to A‐form transition with increasing ionic strength. This property of G‐tracts is directly connected to the observation that cations are preferentially localized in the major groove of G‐tract sequences. Generic DNA, which represents the vast majority of DNA sequences, has a more balanced occupation of the major and minor grooves by cations than A‐tracts or G‐tracts and is thereby stabilized in the canonical B‐form helix. Thus, DNA secondary structure can be viewed as atug of warbetween the major and minor grooves for cations, with A‐tracts and G‐tracts each having one groove that dominates the other for cation localization. Finally, the sequence‐directed curvature caused by A‐tracts and G‐tracts can, in both cases, be explained by the cation‐dependent mismatch of A‐tract and G‐tract helical structures with the canonical B‐form helix of generic DNA (i.e., a cation‐dependent junction model). © 2003 Wiley Periodicals, Inc. Biopolymers 69: 144–159, 2003