bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurospora crassa cydophilins
Authors: Tropschug M
Published: November 2023

Fungi like Neurospora crassa or Saccharomyces cerevisiae are ideal organisms to study the cellular roles of the different peptidyl-prolyl cis-trans isomerases (PPIases) and the molecular mechanisms of action of immunosuppressants like CsA, FK506 or rapamycin (reviewed by Kunz and Hall, 1993). These drugs were originally isolated as antifungal compounds. Three families of PPIases have been described. Two of these, the cyclophilins (Cyps) and FKBPs, have been known for some time (see reviews by Schreiber, 1992; Schmid, 1993; Fischer, 1994; Galat and Metcalfe, 1995; see also the overview in this volume, p. 359). Parvulins constitute a more recently defined family (Rahfeld etal., 1994; see overview p. 365). To date only members of the Cyp (this entry) and FKBP (see entry p. 416) families have been defined in N. crassa.
Drosophila melanogaster Hsc4p
Authors: Mehta A D , Rubin D M , Elefant F , Palter K B
Published: November 2023

The nucleotide sequence for Drosophila HSC4 was determined from a genomic clone [GenBank accession numbers M36114 (Perkins et al., 1990), L01500 (Rubin et al., 1993)]. Comparison of the genomic sequence with that of a cDNA clone revealed the presence of a 1.6-kb intron located 5’ of the initiating ATG (Perkins et al., 1990). The DNA sequence of HSC4 revealed an open reading frame of 1953 bp that would encode a protein of 651 amino acids with a molecular mass of 71 130 daltons.
Saccharomyces cerevisiae FKBP13
Authors: Parent S P , Neilsen J B
Published: November 2023

The yeast FKB2 gene encodes a single open reading frame of 135 amino acids (GenBank accession numbers M90767, M90646; Nielsen et al., 1992; Partaledis et al., 1992). At its start are two consecutive ATG initiator codons. Depending on which start site is used, there is a signal peptide of 16 or 17 amino acids, which is presumably removed by processing. The mature protein is 118 amino acids with a predicted molecular weight of 12 446 daltons. Among the FKBPs, it is most homologous to human FKBP13 (hFKBP13) (Jin etal., 1991), sharing 64% identity in the core regions of these proteins. Its identity with the major human cytosolic FKBP (hFKBP12) in the same region is 51%. The amino acid residues of hFKBP12 and yFKBPI 2, whose side chains interact with FK506, are conserved (Van Duyne etal., 1991; Rotonda et al., 1993).
Saccharomyces cerevisiae Npi46p
Authors: Shan X , Xue Z , Melese T
Published: November 2023

NPI46 was isolated by screening a AZAP yeast genomic expression library, using antiserum raised against yeast NLS-binding proteins (Shan et al., 1994). It encodes a protein of 411 amino acid residues with a molecular mass of 46 541 Da (Genbank accession number X79379). It was also identified as Fpr3, a protein that binds to FK520, a FK506-related immunosuppressant agent (Benton et al., 1994; Manning-Krieg etal., 1994). The C-terminal domain of Npi46p shares 45% identity with both human and yeast FKBP12. The N-terminal domain is highly charged, contains a bipartite NLS, and a number of acidic stretches with serine residues.
Mammalian FKBP12.6
Authors: Wiederrecht G J
Published: November 2023

Among the known mammalian members of the family of FK506-binding proteins, FKBP12.6 is the one most closely related to FKBP12. The affinities of FK506 and rapamycin for FKBP12.6 are equivalent to their affinities for FKBP12. Importantly, the FKBP12.6-FK506 complex is as potent an inhibitor of calcineurin as the FKBP12-FK506 complex, indicating that FKBP12.6 may be associated with some of the immunosuppressive or toxic side effects of FK506 therapy. The physiological function of FKBP12.6 is distinct from that of FKBP12. Whereas FKBP12 binds to and regulates the ryanodine receptor (RyR-1) of skeletal muscle sarcoplasmic reticulum, FKBP12.6 binds to and regulates the ryanodine receptor isoform (RyR-2) of cardiac muscle.
Saccharomyces cerevisiae Ess1
Authors: Hanes S D
Published: November 2023

The ESS1 gene was originally isolated by cross-hybridization with the simian sarcoma virus oncogene v-sis, known to promote the G1/S transition. However, Ess1 protein bears little similarity to p28s/s. ESS1 mapped to the right arm of chromosome 10 and was not allelic to any known yeast mutation (Hanes et al., 1989). PTF1 was identified in a screen for pre-mRNA processing mutants defective in 3’-end formation (Hani etal., 1995).
Transcriptional regulation of eukaryotic heat shock genes
Authors: Morimoto R I
Published: November 2023

Common to all organisms is an essential, highly conserved and exquisitely regulated cellular response to suboptimal physiological and environmental conditions that affect cell growth, maintenance of cellular activities, and development. The activation of heat shock genes is a highly regulated response to heat shock, oxidative stress, heavy metals, various toxic chemicals, bacterial and viral infection, and exposure to a number of acute and chronic disease states which results in the elevated synthesis of a family of stress-induced or heat shock proteins (Lindquist and Craig, 1988; Morimoto et al., 1990, 1994). This affords the cell a protective mechanism against acute exposure to stress which, if unchecked, leads to irreversible cell damage and cell death. Heat shock proteins, many of which have properties as molecular chaperones, have essential roles in the process of protein biosynthesis, specifically in the synthesis, folding, degradation, transport, and translocation of proteins (reviewed in Gething and Sambrook, 1992; Georgopoulos and Welch, 1993; Hendrix and Hartl, 1993; Craig et al., 1993; Morimoto et al., 1994).
Mammalian mitochondrial Hsp70
Authors: Hoogenraad N J , Hoj P B , Naylor D , Webster T
Published: November 2023

Grp 75 (Mizzen et al., 1989); P71 (Leustek et al., 1989); Pbp74 (Domanico et al., 1993); C3H strain specific antigen (CSA) (Michikawa et al., 1993); mortalin (Wadhwa et al., 1993) ;mthsp75 (Bhattacharyya etal., 1995).
Neurospora crassa Hsp88
Authors: Plesofsky-Vig N , Brambl R
Published: November 2023

We first identified Hsp88 in our search for proteins from heat shocked cells that interact with the small HSP of N. crassa. Two detectable proteins, Hsp70, Hsp88, were found to bind specifically to Hsp30 (N. Plesovsky-Vig, R. Brambl, unpublished results). Hsp88 was isolated by affinity chromatography, gel electrophoresis. After digestion of Hsp88 by trypsin, several peptides were N- terminally sequenced, leading to the design of conceptually coding oligonucleotides. An amplified gene fragment, produced by the polymerase chain reaction, was used to probe a N. crassa cDNA library,, a 2.6 kb cDNA was identified, sequenced.
Mammalian OSP94
Authors: Gullans S R , Kojima R
Published: November 2023

osp94 was identified during an analysis of mRNAs that are up-regulated by hyperosmotic stress in mouse inner medullary collecting duct (mlMCD3) cells (Kojima et al., 1996). APG-1 was identified during a search for germ cellspecific mRNAs in testes (Kaneko etal., 1997).
Mammalian Grp170
Authors: Easton D P , Subjeck ,J R
Published: November 2023

Chinese hamster Grp 170 is encoded as a 999 amino acid precursor with a 34 residue signal peptide (GenBank accession number U34206, Chen et al., 1996). The calculated molecular weight of the processed protein is 107 461 Da. Grp170 is a glycoprotein with a calculated Mrof 164 kDa, determined by SDS-gel electrophoresis. The peptide terminates in NDEL which serves as an ER retention signal.
HSP40 (DnaJ-related) proteins — an overview
Authors: Cyr D M
Published: November 2023

The purpose of this overview is to provide an introduction to the key features of the HSP40 or DnaJ family of proteins. General aspects of HSP40 function will be discussed, special features of individual family members will be highlighted. To limit overlap, the details of the functions of specific HSP40 proteins will be discussed in the entries on individual family members. At present there are a total of 219 entries in GenBank, some redundant, for proteins with homology to the progenitor of the HSP40 family, E. coli DnaJ. A limited number of HSP40 proteins from both E. coli, eukaryotic organisms whose sequence, function are known have been selected for detailed discussion below.
Saccharomyces cerevisiae Sisi
Authors: Arndt K T
Published: November 2023

The DNA sequence of SISI (GenBank accession number X58460) predicts a protein of 37.6 kDa with a pl of 9.15, a codon bias of 0.163 (Luke et al., 1991). The N-terminal third, the C-terminal third of Sislp are related to the corresponding regions of bacterial DnaJ. The middle third of Sislp is unrelated to DnaJ, contains a glycine/methionine-rich region.
Saccharomyces cerevisiae Zuotin
Authors: Cyr A M
Published: November 2023

Zuotin was purified from yeast nuclear matrix based on its ability to bind a Z-DNA affinity column (Zhang et al., 1992). The ZUO1 gene (GenBank accession number X63612) is located on yeast chromosome VII near ADE3, encodes a 433 residue protein that has predicted molecular weight of 49 kDa (Zhang et al., 1992). Zuotin is a basic protein with a pl of 8.8 and, based on sequence analysis, has a number of interesting features (Zhang etal., 1992).
Saccharomyces cerevisiae Mdjlp
Authors: Schwarz Schwarz
Published: November 2023

The nuclear gene for mitochondrial DnaJ (MDJ1) was identified during the sequence analysis of chromosome VI (GenBank accession number D50617x53). The MDJ1 open reading frame encodes a polypeptide of 511 residues (Rowley et al., 1994) that possesses all the features characteristic of a DnaJ protein: (i) an N-terminal J-domain of about 70 amino acid residues; (ii) a 60-residue segment rich in glycine, phenylalanine; (iii) four cysteine-containing repeats with the sequence motif: CXXCXGXG (with X being predominantly a polar or charged residue);, (iv) a C-terminal domain with little sequence conservation to other DnaJ proteins (for detailed reviews about the HSP40/DnaJ protein family see Caplan et al., 1993; Cyr et al., 1994;, the introductory overview to this section, p. 89).
Saccharomyces cerevisiae Scjlp
Authors: Craig E A
Published: November 2023

Saccharomyces cerevisiae DnaJ homologue (Blumberg, Silver, 1991). SCJ1 was originally identified by a genetic screen in yeast in which overexpression of candidate genes could result Brodsky, J.L., Schekman, R. (1993). A sec63-BiP complex from yeast is required for protein translocation in a reconstituted proteoliposome. J. Cell Biol. 123, 1355-1363.
Plant Anj1
Authors: Zhu J -K
Published: November 2023

The nucleotide sequence of ANJ1 cDNA cloned from the halophytic higher plant Atriplex nummularia (GenBank accession number L09124) predicts a polypeptide of 417 amino acids without signal sequence or transmembrane domain (Zhu et al., 1993a). At the N-terminus is a J-domain of approximately 70 amino acids which is conserved in all DnaJ-related proteins from both prokaryotes, eukaryotes (Caplan et al., 1993; Zhu et al., 1993a). J-domains are known to interact with HSP70 homologs (Schlenstedt et al., 1995). A glycine-rich motif (or G/F domain) (Wall et al., 1995) connects the J-domain to a putative ‘zinc finger’ which consists of four CXXCXGXG repeats (Caplan et al., 1993; Zhu et al., 1993a).
Escherichia coli GrpE
Authors: Buchberger A , Bukau B
Published: November 2023

The first grpE mutation, grpE280, was obtained upon selection for mutants resistant to lytic infection by bacteriophage A (Saito, Uchida, 1977). The grpE gene product was later shown to be identical to heat shock protein B25.3 (Ang etal., 1986).
Drosophila melanogaster Hsp83
Authors: Nathan D F , Lindquist S
Published: November 2023

Drosophila melanogaster HSP83 is a single copy gene positioned at cytogenic locus 63B (GenBank accession numbers X03810, K01685). Unlike the majority of Drosophila HSP genes, which do not contain intervening sequences, the HSP83 gene contains an intron just upstream of the translation start site (Hackett, Lis, 1983; Blackman, Meselson, 1986). The second exon encodes a 718 amino acid protein that is highly homologous to other members of the HSP90 family.
Plant Hsp90
Authors: Krishna P
Published: November 2023

Nucleotide sequence analysis of plant hsp90 genes (GenBank accession numbers M36960, M96549, M99431) predicts a molecular mass between 80, 82 kDa,, pls of 5.73, 5.76 in two cases, for the encoded proteins (Conner et al., 1990; Felsheim, Das, 1992; Koning et al., 1992; Takahashi et al., 1992; Marrs et al., 1993; Yabe et al., 1994).
The CPN60, CPN10 families — an overview
Authors: Hartl F U , Mayhew M
Published: November 2023

CPN60 (or chaperonin 60; Hemmingsen et al., 1988) family members are also called HSP60. CPN10 family members are also called chaperonin 10, HSP10 or cochaperonin. Sequence alignment of CPN60 family members reveals at least 70% similarity, 50-70% identity between any two members. Residues 86-91 of the CPN60 protein from Escherichia coli, GroEL, form part of the ATP-binding site that includes the consensus sequence GDGTT found in all chaperonins, which is similar to the sequence GXGXX(G) in the ATP-binding sites of many type I kinases (Kim et al., 1994). Finally, all CPN60 family members contain two or three GGM repeats at their extreme C-termini.
Thermus thermophilus GroEL, GroES
Authors: Taguchi H , Yoshida M
Published: November 2023

Thermus chaperonin means the chaperonin from T. thermophilus, consisting of 14 copies of GroEL homologues (T. th cpn60), seven copies of GroES homologues (T. th cpn10) (Taguchi etal., 1991; Amada etal., 1995).
The neuroendocrine polypeptide 7B2
Authors: Martens GJ
Published: November 2023

The 7B2 protein was first isolated from porcine, human pituitary glands by HPLC,, the first 50 (porcine), 77 (human) amino acid residues were determined by N-terminal amino acid sequence analysis (Hsi etal., 1982; Seidah etal., 1983).
CCTγ
Authors: Kubota A , Willison K
Published: November 2023

A temperature-sensitive mutant called bin2-1 shows abnormal actin, tubulin organization in budding yeast, disruption of the gene creates a recessive lethal phenotype (Chen et aL, 1994). A temperature-sensitive mutant of CCTy is lethal in combination with a temperature-sensitive mutant of either CCTa, CCT/3 or CCT5 (Chen etal., 1994).
Escherichia coli CIpX
Authors: Wawrzynow A , Zylicz M
Published: November 2023

The clpX gene (GenBank accession number 223278) together with the dpP gene forms a heat shock-regulated operon located upstream of the Ion gene at 10 minutes on the E. coli map (Gottesman et al., 1993). clpX can also be expressed independently from dpP using its own promotor (Yoo et al., 1994). The clpX gene encodes a protein of 424 amino acids (Gottesman et al., 1993). The clpX gene was identified following N-terminal sequence analysis of the ClpX (LopC) protein, which is the specificity component of CIpXP ATP-dependent protease (Wojtkowiak et al., 1993).
Ca2+ -ATPase (plasma membrane)
Authors: Celio Marco R
Published: November 2023

The plasma membrane Ca2+ ATPase (PMCA) or Ca2• pump is an integral membrane protein which is present in all mammalian cells. It belongs to the family of the P-type ATPases. The pump transports Ca2+ ions out of the cells, by using the energy stored in ATP and is essential in the control of the Ca2+ concentration in the cytosol.
α-Toxin (Staphylococcus aureus)
Authors: Menestrina G , Ferreras) M
Published: November 2023

Staphylococcal a-toxin is an exotoxin with hemolytic, cytotoxic, dermonecrotic, and lethal activity (Thelestam and Blomqvist 1988; Bhakdi and Tranum-Jensen 1991). It is secreted by most pathogenic strains of S. aureus (commonly Wood 46) as a water-soluble polypeptide of 33 kD (293 amino acid residues, sequence accession number to the Swiss Prot databank: P09616 HLA-STAAU; corrections were published (Walker et al. 1992)). Its relevance as a virulence factor has been firmly established, at least in animal models. As outlined in Fig. 1, this toxin oligomerizes on the surface of mammalian cells (and liposomes) to form a membrane-embedded oligomer of about 220 kD, which appears in the electron microscope as a hollow cylinder protruding from the plane of the bilayer. It forms crystalline 2D layers on lipid membranes of either natural or artificial origin. From such arrays, a low-resolution three-dimensional map of the oligomer was obtained (Olofsson et al. 1988), suggesting it was a hexamer. However, more recent low-resolution X-ray analysis of microcrystals (Gouaux et al. 1994) provided evidence that the oligomer is actually an heptamer like the one formed by aerolysin from Aeromonas hydrophila.
δ-Toxin (Staphylococcus aureus) and melittin (Apis mellifera)
Authors: Dufourcq J , Castano S
Published: November 2023

δToxin and melittin (Mel) are 26 residue long peptides, secreted by Staphylococcus aureus strains and representing about 50 per cent of the dry weight of bee venom, respectively. Both are pleiotropic toxins with no sequence homology, despite this they share most of their biological properties. The first target is the plasma membrane, but the toxins also act on a wide variety of intracellular elements whether membranes, proteins, or nucleic acids. Their behaviour is dominated by their amphipathic character, they are surface active, have rather nonspecific affinity for interfaces, and are classified as ‘membrane invading’ or ‘direct lytic’ peptides.
Aerolysin (Aeromonas hydrophila)
Authors: Buckley J T
Published: November 2023

Aerolysin is secreted as a 52 kDa protoxin by Aeromonas sp. (see van der Goot et al. 1994, for a recent review). The protein appears to be primarily responsible for the patho¬ genicity of A. hydrophila to mice (Chakraborty et al. 1987). The aerA structural genes from a number of differ¬ ent species have been sequenced, and the structure of the protein from A. hydrophila has been solved (Parker et al. 1994). The protein is a dimer in the crystal as well as in solution and each polypeptide chain contains four domains. More than 70 per cent of the molecule is in β-sheet. The protoxin is converted to the active toxin by proteolytic removal of approximately 43 amino acids from the (-terminus (Howard and Buckley 1985; van der Goot et al. 1992). This can be accomplished by proteases secreted by the bacteria, as well as by mammalian proteases such as trypsin, chymotrypsin, and furin.
Anthrax edema factor (Bacillus anthracis)
Authors: Leppla S H
Published: November 2023

Anthrax edema factor (EF, originally designated Factor I) is a calmodulin-dependent adenylyl cyclase (Leppla 1982) which is one of the three proteins of the anthrax toxin complex (Smith et al. 1955; Leppla 1991a; 1995). The EF gene (Escuyer et al. 1988; Mock et al. 1988; Robertson et al. 1988; Tippetts and Robertson 1988) (GenBank accessions M23179 and M24074), located on the large pXO1 plasmid, encodes a precursor of 800 amino acids. Cleavage of the 33-amino acid signal peptide produces the 767 residue mature protein (PIR Protein database accession JS0029) having a mass of 88.8 kDa. The other proteins of the toxin complex are protective antigen (PA, GenBank M22589) and lethal factor (LF, GenBank M29081 and M30210; see separate entry in this book p. 00). None of the three proteins contain cysteine. As shown in Fig. 1, EF enters cells by binding to proteo¬ lytically activated, receptor-bound PA (Klimpel et al. 1992). EF (or LF) is then endocytosed and translocated from endosomes directly to the cytosol of cells, where it produces unregulated high concentrations of cAMP (Leppla 1982; Gordon et al. 1988). Entry of EF and LF is totally dependent on PA. The receptor for PA is unknown, but is present on nearly all types of cells (Escuyer and Collier 1991; Leppla 1991a).
Ribosome-inactivating proteins
Authors: Stirpe F
Published: November 2023

Ribosome-inactivating proteins (RIPs, review by Barbieri et a/. 1993) are a class of proteins present in various tissues of several plants which inactivate mammalian ribosomes and, with less activity and to variable extent, plant, fungal, and bacterial ribosomes. They are enzymes, N-glycosidases, which release adenine from rRNA. They are divided into two groups: type 1, consisting of a single peptide chain, and type 2, in which an A chain with enzymatic activity is linked to a slightly larger B chain with the properties of a galactosyl-specific lectin. The B chain binds to galactosylterminated receptors on the membrane of most animal cells, allowing the molecule to enter the cytoplasm. Thus most type 2 RIPs are potent toxins, ricin being the best known, although recently some nontoxic lectins with the structure of type 2 RIPs have been described. Type 1 RIPs do not enter easily into cells, and consequently are much less toxic than type 2 RIPs.
Enterotoxin A and cytotoxin B (Clostridium difficile)
Authors: Eichel-Streiber C Von
Published: November 2023

The enterotoxin A (TcdA) and the cytotoxin B (TcdB) of Clostridium difficile are the two virulence factors respons¬ ible for the induction of antibiotical associated diarrhea (AAD) or pseudomembranous colitis (PMC) (Lyerley et al. 1988; Knoop et al. 1993). Diagnosis of the disease is done by identifying the toxins in stool specimens.The high molecular weight cytotoxins are secreted by the bacterium into its culture supernatants from which they may be isolated. One high producer (Sullivan et al. 1982), C. difficile VPl10463 (see Table 1), is used in many laboratories.
IcsA (Shigella flexneri)
Authors: Egile C , Sansonetti P J
Published: November 2023

Shigella flexneri, the causative agent of bacillary dysentery, is a facultative intracellular pathogen that can enter and spread inside the host epithelial cells. This invasion process involves a sequence of molecular interactions between bacterial virulence factors and the host cell cytoskeleton (Sansonetti et al. 1994).
Pyrogenic exotoxins (superantigens) (Staphylococcus aureus and Streptococcus pyogenes)
Authors: Fleischer B
Published: November 2023

The members of the pyrogenic exotoxin family are listed in Table 1 (reviewed in Fleischer 1995). The staphylococcal enterotoxins SEA to SEE have been divided into serotypes by antisera, there are three subtypes of SEC (SEC1, SEC2 and SEC3). Recently, SEG and SEH have been cloned. Sequencing of genes of different isolates has shown a marked microheterogeneity due to mutations. Other members of the family are the streptococcal toxins SPEA and SPEC (also designated as erythrogenic toxins) and the streptococcal superantigen SSA. These molecules consist of a single chain of approximately 230 AA, with one central disulphide bond, they have more or less extensive homologies within the family (Betley et al. 1992). Many of them are encoded on mobile genetic elements. The structure of TSST-1 (originally designated SEF) differs, it has 194 AA and no cysteins. It has only a very low homology to the other toxins but its 3D-structure is very similar (Kim et al. 1994).
Introduction
Authors: Montecucco C , Rappuoli R
Published: November 2023

Life of eukaryotic cells is made possible by an intense vesicular membrane traffic, highly organized in terms of space and kinetics. Ligands, ions, fluids, and portions of the plasma membrane are continuously taken into the cell via endocytosis, and are then addressed to different destinations via sorting compartments. Conversely, proteins, lipids, and glycoconjugates, synthetized in the endoplasmic reticulum and modified in the Golgi apparatus are addressed to their intracellular destination, or are packed inside vesicles for export. Exocytosis can be constitutive for molecules that are to be exported at a basal rate, or regulated for molecules that are to be released in response to appropriate stimuli. The most finely tuned exocytic process is the release of neurotransmitter at the presynaptic membrane. Neurotransmitter is contained within small synaptic vesicles of similar size (about 50 nm in diameter) which are packed at synaptic terminals. The large majority of these vesicles are bound to the cytoskeleton and are not available for immediate release. Some vesicles are bound to the cytosolic face of the presynaptic membrane at active zones which include voltage gated calcium channels. They are ready to release their content in the intersynaptic space. However, at micromolar calcium, only occasionally one of them fuses with the presynaptic membrane, giving rise to a mepp (miniature end plate potential). The membrane depolarization that is at the basis of the transmission of the nerve impulse, opens presynaptic calcium channels. This leads to a local increase of calcium concentration which triggers, within 100-300 µs, the fusion of the synaptic vesicle with the plasma membrane, with the ensuing release of neurotransmitter. The proteins involved in the docking-priming-fusion of small synaptic vesicles with the presynaptic membrane are being characterized.
VAMP-specific botulinum neurotoxins
Authors: Schiavo G
Published: November 2023

Botulinum neurotoxins (BoNT A-G) are the causative agents of the flaccid paralysis of botulism (Hatheway 1995) and are produced by toxigenic strains of Clostridium botulinum and less frequently Cl. barati and Cl. butyricum (Hall et al. 1985; Aureli et al. 1986). BoNTs are produced as a large complex of 300-900 kDa con¬ taining the neurotoxin (150 kDa) and additional components, such as hemagglutinin (300 kDa) and a nontoxic peptide (Sakaguchi 1983). These additional proteins play a role in the stabilization of the neurotoxins to the gut is activated by proteolysis at an exposed loop, generating the active di-chain form of the toxin (DasGupta 1994). This form is composed of the heavy chain (H, 100 kDa) responsible for the interaction of the toxin to specific receptor(s) present at the neuromuscular junction and for the translocation of the light chain (L, 50 kDa) into the cytoplasm. A critical step for the activation of the zinc-endopeptidase activity of the L chain is the reduction of the interchain disulfide bridge (Montecucco and Schiavo 1995).
Introduction
Authors: Pongs O
Published: November 2023

The purpose of this introduction is to outline briefly what some of the peptide toxins may have in common in terms of their structure and function, and to discuss their usefulness as tools in studying K channel function. According to their relatedness in primary sequence, five different peptide-toxin families may be recognized: the apamin family containing members isolated from bee venoms, the charybdotoxin family isolated from scorpion venoms, the dendrotoxin family isolated from snake venoms, the hanatoxins isolated from spider venom, and the sea anemone toxins. It is obvious that the families have been given nonsystematic and sometimes whimsical names which say more about the original discoverers of the peptide toxins than about the molecules themselves. Because of this unsatisfactory situation, C. Miller recently suggested in his excellent review on the structure and function of the charybdotoxin family of K channel¬ blocking peptides a formalized nomenclature (Miller 1995). In analogy to the now widely accepted K channel nomenclature, he proposed to abbreviate K channel¬ blocking peptide toxins as K-toxins (KTx) and in particular the charybdotoxin family members as a-KTxm. n, where m refers to the subfamily and n to the member within the given subfamily. For example, a-KTx1.1 would be charybdotoxin, a-KTx2.1 noxiustoxin etc. as outlined in Table 2 below.
β-Leptinotarsin-h
Authors: Washbourne P
Published: November 2023

β-Leptinotarsin-h is a toxic protein present in the hemolymph of the potato beetle, Leptinotarsa haldemani. The analogous protein, β-leptinotarsin-d, from L. decemlineata, the Colorado potato beetle, is also toxic, but to a lesser extent and so most studies have used the h-type. Purification and SDS-PAGE shows that the proteins have molecular weights of around 57 and 45 kiloDaltons, respectively. Bidimensional PAGE with isoelectric focusing indicate that the protein is slighty acidic (Crosland et al. 1984). Neither the protein nor the gene has been sequenced.Intoxication can only occur when injected; oral ingestion causes no effect, thus it is probable that the protein does not play a defensive role for the potato beetle. Injection of the protein into the thorax of insects causes them to become sluggish, their limbs to become rigid and spread and finally causes death. In vertebrates, symptoms include partial paralysis, decrease in breathing rate, convulsions, and lethargy leading to death (Hsiao and Fraenkel 1969).
Toxin a (‘Naja nigricollis’)
Authors: Ménez A
Published: November 2023

The cobra snakes of the species Naja (Elapidae) produce potent venoms with which they subdue their prey. Among the most toxic components are the curaremimetic toxins which provoke flaccid paralysis and death, as a result of respiratory failure. Detected by Boquet and coworkers (1966), Eaker and Porath showed, in 1967, that toxin a possesses a single chain of 61 amino acids with four disulfides. Toxin a is currently isolated from venom of an African spitting cobra originally named Naja nigricollis (Boquet et al. 1966). Further taxonomical studies suggested that the snake should be named Naja mossambica pa/Iida (Fryklund and Eaker 1975) and more recently Naja pa/Iida (B. Hughes, personal communication). Toxin a was radioactively labelled by replacing a proton of histidine 31 by an atom of tritium, using a procedure based on catalytic deshalogenation (Menez et al. 1971).
Introduction
Authors: Treves S , Zorzato F
Published: November 2023

Ca2+ release from intracellular stores plays an important role in the regulation of numerous cellular functions ranging from muscle contraction to cell division and neurotransmitter release. The intracellular Ca2+ stores of excitable and nonexcitable cells utilize one or two of the intracellular Ca2+ channels to release Ca2+ upon cell stimulation, namely the ryanodine and the inositol 1,4,5-trisphosphate receptors (Berridge 1993).The mammalian ryanodine receptor (RYR) is a large tetrameric oligomer made up of four subunits of 560 kDa, which migrate as a single protein in 5D5- polyacrylamide gel electrophoresis (Pessah et al. 1986; lmagawa et al. 1987; Lai et al. 1988). The purified RYR complex also contains the FK-506 binding protein, a protein of 12 kDa, which is tightly associated to the RYR promoter with a stoichiometric ratio of 1:1 (Jayaraman et al. 1992). Experimental evidence has demonstrated the existence of three distinct isoforms which are preferentially expressed in skeletal muscle, heart, and brain, respectively.
Equinatoxins (Actinia equina L., sea anemone)
Authors: Maček P
Published: November 2023

Equinatoxins I, 11, and Ill (EqTx) are lethal and cytolytic 19 kDa polypeptides (Macek and Lebez 1988) belonging to a larger family of pore-forming toxins from sea anemones (Actiniaria) (see reviews Kem 1988; Turk 1991; Macek 1992). The most abundant isoform, equinatoxin II (synonym: equinatoxin; Ferlan and Lebez 1974), is a single chain, 179 amino acids long, without cysteine (Belmonte et al. 1994). EqTx II is nearly identical to tenebrosin-C from A. tenebrosa (Simpson et al. 1990; Norton et al. 1992) (sequences in Swiss Prot Databank: P17723 TENC_ACTTEX; Genbank: U41661).
Synemin
Authors: Bellin Robert M , Sernett Suzanne W , Robson Richard M
Published: November 2023

Synemin is a very large (230 kDa as judged by SDS-PAGE and 186 kDa by sequencing) intermediate filament (IF) protein that is found with desmin and/or vimentin in embryonic and mature smooth and striated muscle cells, and in a small number of non-muscle cells such as avian erythrocytes and lens. In mature striated muscle cells, synemin is localized with desmin in a collar-like pattern around the periphery of the myofibrillar Z lines where its proposed role is to help desmin IFs link other cytoskeletal structures such as adjacent myofibrils, and the peripheral layer of myofibrils to the sarcolemma.
Filaggrins
Authors: Dale Beverly A , Presland Richard B
Published: November 2023

Filaggrin is named for its ability to cause intermediate filament aggregation in vitro. It is one of the original proteins recognized as an ‘intermediate filament-associated protein’ or IFAP. Filaggrin is expressed by keratinocytes of epidermis and other cornified epithelia as the cells undergo terminal differentiation and form the protective surface layers of the body. It is a cationic protein that is derived from an inactive precursor, profilaggrin, which is insoluble, highly phosphorylated, contains multiple copies of filaggrin, and is processed enzymatically by phosphatases and proteases to the soluble, mature filaggrin.
Lamin-associated proteins
Authors: Gerace Larry , Yang Li
Published: November 2023

Lamin-associated proteins (LAP) comprise a group of polypeptides localized at the inner nuclear membrane which interact stably with nuclear lamins. The three lamin-associated proteins that have been characterized in detail, LAP1, LAP2, and LBR, are all integral membrane proteins, and have potential roles in the attachment of nuclear lamins and/or chromatin to the inner nuclear membrane.1 Another integral membrane protein, emerin, has recently been demonstrated to be a LAP.24
Plectin
Authors: Wiche Gerhard
Published: November 2023

Plectin is a versatile cytoskeletal linker protein of high molecular weight (>500 000 Da) that is abundantly expressed in a wide variety of mammalian tissues and cell types. It interacts with all major cytoskeletal filament networks and is a major constituent of plasma membrane-associated junctional complexes (e.g. hemidesmosomes of epithelia, Z lines, dense plaques and intercalated discs of various types of muscle, and focal contacts). Plectin molecules seem to play an important role in strengthening cells and tissues against mechanical stress, as recently confirmed by findings that link defective plectin expression to human disease (epidermolysis bullosa simplex with muscular dystrophy) and by the observation of similar phenotypes in plectin gene knockout mice. An emerging concept postulates tissue-specific expression of functionally different isoforms of the protein.
Dynein, axonemal
Authors: Gibbons Ian R
Published: November 2023

Axonemal dynein forms a double row of projections, the outer and inner arms, that are attached to the A tubule of each axonemal doublet and extend toward the B tubule of the adjacent doublet.10 The outer dynein arms are distributed along the length of the A tubule, with a constant spacing of 24 nm. The arrangement of inner dynein arms is more complex, with three distinct species of inner arm that are distributed along each A tubule in unevenly spaced triplets.
Dynein, cytoplasmic
Authors: Vallee Richard
Published: November 2023

Cytoplasmic dynein is a large, two-headed ATPase which produces force along microtubules in the retrograde direction (toward the microtubufe minus end). It is involved in a wide range of functions, including retrograde axonal transport and mitosis, and it associates with numerous subcellular structures, including kinetochores and a variety of membrane-bounded organelles.
Myosin, plant
Authors: Kendrick-Jones John , Reichelt Stefanie
Published: November 2023

In plant cells, myosins are believed to play key roles in such prominent actin-based movements as cytoplasmic streaming and directed vesicle transport. Although immunological and biochemical studies have indicated the existence of myosin-like proteins in plants but compared to animal/protozoan myosins little is known about these plant proteins. Recently, 16 plant myosin genes belonging to three unique classes have been cloned and sequenced from various species including Arabidopsis, Helianthus, Acetabularia, and Chlamydomonas.
Dynactin complex
Authors: Schroer Trina A
Published: November 2023

The dynactin molecule as a unit appears to be unique, though it is structurally similar to the short actin filaments that comprise the erythrocyte membrane cytoskeleton. This has led to speculation that the dynactin Arp1 filament might bind membranes via a spectrin network.
Auxilin
Authors: Ungewickell Ernst
Published: November 2023

Auxilin is a specialized member of the DnaJ protein family and functions as an essential cofactor to HsclO in the uncoating of clathrin coated vesicles. Auxilin associates preferentially with polymeric clathrin and captures with its carboxyl-terminal J domain the uncoating protein HsclO. Upon ATP hydrolysis, HsclO is transferred to clathrin which dissociates subsequently as a clathrin-HsclO complex from the vesicle membrane. This complex no longer contains auxilin.
Clathrin
Authors: Brodsky Frances M
Published: November 2023

Clathrin is a triskelion-shaped, self-assembling protein which polymerizes into a polyhedral lattice on the cytoplasmic surface of cellular membranes. Formation of the clathrin lattice constitutes a mechanism for sorting membrane-associated proteins which are incorporated into the lattice via bridging proteins, known as adaptors or assembly polypeptides, which interact both with clathrin and transmembrane proteins. Clathrin-coated vesicles are thereby responsible for receptor-mediated endocytosis, for sorting proteins in the trans-Golgi network during lysosome formation, and for membrane sorting during secretory granule maturation.
GM130
Authors: Lowe Martin , Nakamura, Nobuhiro , Warren Graham
Published: November 2023

GM130 was originally identified as a 130 kDa component of a Golgi matrix fraction prepared by extraction of purified rat liver Golgi membranes with Triton X-100 in low salt .
ERM proteins: ezrin, radixin, and moesin
Authors: Bretscher Anthony , Berryman Mark
Published: November 2023

Ezrin was also known as cytovillin until the identity of the two proteins was appreciated. The N-terminal ∼300 residues show ∼35 per cent identity to the corresponding domain of erythrocyte band 4.1, which defines members of the band 4.1 superfamily. Other members include talin, merlin, and several protein tyrosine phosphatases.
Filamin
Authors: Hock Rick S
Published: November 2023

Filamin, a major component of the microfilament network, plays a critical role in determining the three-dimensional arrangement of actin filaments in vivo and in vitro (reviewed in ref. 1). This actin-cross-linking protein was first isolated from avian smooth muscleand has been purified from many sources including platelets, macrophages, guinea-pig vas deferens, baby hamster kidney (BHK-21) cells, thyroid gland, Hela cells, and motile Dictyostelium amoebae. Filamin is now known to exist in most cell types as a family of isoforms. The number of isoforms has not been defined, although multiple isoforms are apparently present within a single human cell type, Hela cells. Also, isoform switching occurs during myogenesis.
Marcks family
Authors: Aderem Alan
Published: November 2023

MacMARCKS/MRP is the only known MARCKS homologue (see below). However, a number of proteins contain domains that are homologous to the effector domain of MARCKS. These include GAP-43 (neuromodulin), ankyrin, gravin, and diacylglycerol kinase zeta.
p58gas
Authors: Carraway Coralie A Carothers , Carraway Kermit L
Published: November 2023

Binding studies on purified or in vitro translated p58gas are also consistent with this role. It will bind F-actin, but not G-actin.1 Under actin polymerizing conditions p589a9 acts as a capping protein without severing activity. It will bind phospholipid vesicles with little head group specificity, probably due at least in part to fatty acid linked to the N-terminal glycine myristoylation site.
Ponticulin
Authors: Luna Elizabeth J
Published: November 2023

Although an immunologically cross-reactive protein of similar size has been observed in human polymorphonuclear leukocytes, only ponticulin from the soil amoeba, Dictyostelium discoideum, has been characterized. Purified Dictyostelium ponticulin consists of six major 17-kDa isoforms with pis ranging from 4.2 to 5.2 on two-dimensional SDS-PAGE. In addition, minor polypeptides at 19 kDa (five isoforms, p/ range 4.4 to 5.2) and 15 kDa (two isoforms, pl’s 4.3 and 4.7) co-isolate with ponticulin on F-actin affinity columns. Because all these isoforms are absent from cells in which the single-copy gene encoding ponticulin has been disrupted, the ponticulin isoforms appear to arise from differential post-translational processing.
Profilins
Authors: Pollard Thomas D
Published: November 2023

The following provides details about the biochemical activities of profilins. In addition to these interactions, plant profilins are major human allergens. With the interesting exception of vaccinia virus profilin, all well characterized profilins bind actin monomers with micromolar affinity. New spectroscopic assays indicate that Kds for profilins binding Mg-ATP actin (the form in the cytoplasm) are in the range of 0.1 to 0.5 µM. The major contact site in cocrystals of actin and profilin28 is the binding site in solution.
Scryin
Authors: Way Michael
Published: November 2023

Scruin is a 102 kDa actin bundling protein found in the acrosomal process of Limulus sperm, and which is present in a 1:1 molar ratio with actin. The protein consists of two homologous domains, which are predicted to have super-fl-barrel folds, connected by a 200 amino acid residue linker region. Scruin is also complexed with calmodulin, implicating a possible calcium-induced conformational change in scruin during the extension of the acrosomal process.
Slalp
Authors: Ayscough Kathryn R , Drubin David G
Published: November 2023

Sla1p is a protein that immunolocalizes to the cortical actin cytoskeleton in the budding yeast Saccharomyces cerevisiae. Deletion of the gene encoding Sia1p causes a disruption of the actin cytoskeleton and cells become temperature-sensitive for growth. Sia1p contains three SH3 domains at its N terminus, while its C-terminus is characterized by the presence of repeats rich in glycine, praline, and glutamine residues. A full-length homologue of Sia1p has now been identified in the fission yeast, Schizosaccharomyces pombe.
Sla2p
Authors: Cope M J T V , Drubin David G
Published: November 2023

Sla2p is a protein required for the proper organization of the S. cerevisiae actin cytoskeleton. lmmunolocalization indicates that Sla2p is found in cortical structures. These structures generally, but not exclusively, coincide with the actin patches that are proposed to be involved a variety of essential cellular processes such as exo-and endocytosis, as well as osmotic sensing and cell polarity determination. Mutations in the SLA2 gene result in defective cellular morphogenesis, loss of polarization of actin patches, loss of bipolar budding pattern in diploid cells, reduced or no endocytosis and, in certain yeast strains, death.
Tensin
Authors: Lin Shin , Lin Diane C
Published: November 2023

No synonymous names, but tensin does have many regions showing sequence homology with other proteins.

The discovery of tensin stems from studies on the interaction of F-actin with vinculin, a protein found at focal adhesions of fibroblasts. In experiments in the early 1980s, vinculin preparations from chicken gizzard inhibited actin polymerization in a manner suggesting a direct interaction of the protein with the barbed ends of actin filaments (i.e. capping activity). Subsequent studies indicated that this phenomenon is attributable to the activity of a heterogeneous group of peptides (designated HA1; M, = 20-45 kDa) contaminating the vinculin preparations.
VASP
Authors: Reinhard Matthias , Jarchau Thomas , Reinhard Kathrin , Walter Ulrich
Published: November 2023

VASP, a praline-rich protein substrate of both cAMP- and cGMP-dependent protein kinases, is expressed in most mammalian cell types and tissues. Particularly high VASP levels are detected in human platelets. In cultured cells, VASP is associated with focal adhesions, cell-cell contacts, microfilaments, and highly dynamic membrane regions such as the leading edge. From in vitro binding data VASP has been suggested to link profilin to zyxin, vinculin, and the Listeria spp. surface protein ActA. Functional evidence indicates that VASP is a crucial factor involved in the enhancement of actin filament formation.
Vitamin D-binding/Gc protein
Authors: Haddad John G , Cooke Nancy E
Published: November 2023

This plasma a-globulin is in the albumin, a-fetoprotein family and is synthesized predominantly in the liver. It circulates at a 20-fold higher titre than its mot/mot, vitamin D sterol-ligands, thereby providing their conservation, solubility, and transport in the blood. The protein also binds globular actin at high affinity and constitutes, along with gelsolin, a plasma-actin-scavenger system. Cell surface associations and metabolism of the protein suggest its cellular entry into phagolysosomes, although its direct cellular injection causes a reversible disassembly of microfilaments. Preliminary findings suggest that this protein’s absence in an experimental murine null homozygote can lead to abnormalities in monocytelmacrophage development and activation, as previously suggested by its behaviour as a co-chemotaxin and macrophage activator.
Structural features of IF proteins
Authors: Parry David A D
Published: November 2023

Intermediate filaments (IF), a constituent of almost all eukaryotic cells, are one of three major classes of intra-cellular filaments, the others being the microtubules (about 25 nm in diameter) and the actin-containing microfilaments (about 10 nm in diameter). Initially, the intermediate filaments (IF) were thought to be intermediate in size between the microtubules and the micro-filaments, hence their name, but subsequent structural characterization showed that discrimination on the basis of size was uncertain since IF and microfilaments have similar diameters. Intermediate filaments are not restricted to the cytoplasm but are found also within the nuclear envelope. Generally, however, long sinuous bundles of IF extend from the outer surface of the cell nucleus to the adhesion plaques or desmosomes on the inner surface of the cell membrane.
Desmin
Authors: Ip Wallace
Published: November 2023

Desmin belongs to the intermediate filament family of proteins. Protein sequence homology and intron placement of the desmin gene classify desmin as a type Ill IF protein, together with vimentin, peripherin, and giial fibrillary acidic protein.
Lens beaded filament proteins
Authors: Quinlan Roy A
Published: November 2023

The lens beaded filaments are specific to the lens. As the name suggets, the filaments have a characteristic morphology with 15-20 nm beads decorating a 5-6 nm backbone. The filaments comprise two lens-specific intermediate filament proteins, CP49 (also called phakanin) and filensin along with a-crystal/in particles. Fifensin and CP49 require each other for assembly. The classification of filensin and CP49 into the established intermediate filament types 1-V has not been possible because of a lack of a consensus from gene structure, assembly properties, and sequence homology data. Filensin and CP49 are useful markers for the lens cell fibre cell differentiation. A unequivocal role in lens function has yet to be shown but filensin expression is severely affected in the mouse inherited cataract mutant Elo. Also, lens fibre cell denucleation, an essential step in establishing lens transparency, coincides with the spatial reorganization of the CP49/filensin networks in lens fibre cells and includes the specific entry of CP49 into the nuclear compartment.