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Diverse Proteins (diverse + protein)
Selected AbstractsA semiempirical free energy force field with charge-based desolvationJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 6 2007Ruth Huey Abstract The authors describe the development and testing of a semiempirical free energy force field for use in AutoDock4 and similar grid-based docking methods. The force field is based on a comprehensive thermodynamic model that allows incorporation of intramolecular energies into the predicted free energy of binding. It also incorporates a charge-based method for evaluation of desolvation designed to use a typical set of atom types. The method has been calibrated on a set of 188 diverse protein,ligand complexes of known structure and binding energy, and tested on a set of 100 complexes of ligands with retroviral proteases. The force field shows improvement in redocking simulations over the previous AutoDock3 force field. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007 [source] Disruption of structural and functional integrity of ,2 -macroglobulin by cathepsin EFEBS JOURNAL, Issue 6 2003Mitsue Shibata ,2 -Macroglobulin (,2M) is an abundant glycoprotein with the intrinsic capacity for capturing diverse proteins for rapid delivery into cells. After internalization by the receptor- mediated endocytosis, ,2M-protein complexes were rapidly degraded in the endolysosome system. Although this is an important pathway for clearance of both ,2M and biological targets, little is known about the nature of ,2M degradation in the endolysosome system. To investigate the possible involvement of intracellular aspartic proteinases in the disruption of structural and functional integrity of ,2M in the endolysosome system, we examined the capacity of ,2M for interacting with cathepsin E and cathepsin D under acidic conditions and the nature of its degradation. ,2M was efficiently associated with cathepsin E under acidic conditions to form noncovalent complexes and rapidly degraded through the generation of three major proteins with apparent molecular masses of 90, 85 and 30 kDa. Parallel with this reaction, ,2M resulted in the rapid loss of its antiproteolytic activity. Analysis of the N-terminal amino-acid sequences of these proteins revealed that ,2M was selectively cleaved at the Phe811-Leu812 bond in about 100mer downstream of the bait region. In contrast, little change was observed for ,2M treated by cathepsin D under the same conditions. Together, the synthetic SPAFLA peptide corresponding to the Ser808,Ala813 sequence of human ,2M, which contains the cathepsin E-cleavage site, was selectively cleaved by cathepsin E, but not cathepsin D. These results suggest the possible involvement of cathepsin E in disruption of the structural and functional integrity of ,2M in the endolysosome system. [source] FHA Domains as Phospho-Threonine Binding Modules in Cell SignalingIUBMB LIFE, Issue 1 2003Andrew Hammet Abstract Forkhead-associated (FHA) domains are present in <200 diverse proteins in all phyla from bacteria to mammals and seem to be particularly prevalent in proteins with cell cycle control functions. Recent work from several laboratories has considerably improved our understanding of the structure and function of these domains that were virtually unknown a few years ago, and the first disease associations of FHA domains have now emerged. FHA domains form 11-stranded beta-sandwiches that contain some 100-180 amino acid residues with a high degree of sequence diversity. FHA domains act as phosphorylation-dependent protein-protein interaction modules that preferentially bind to phospho-threonine residues in their targets. Interestingly, point mutations in the human CHK2 gene that lead to single-residue amino acid substitutions in the FHA domain of this cell cycle checkpoint kinase have been found to cause a subset of cases of the Li-Fraumeni multi-cancer syndrome. IUBMB Life, 55: 23-27, 2003 [source] Cone arrestin binding to JNK3 and Mdm2: conformational preference and localization of interaction sitesJOURNAL OF NEUROCHEMISTRY, Issue 3 2007Xiufeng Song Abstract Arrestins are multi-functional regulators of G protein-coupled receptors. Receptor-bound arrestins interact with >30 remarkably diverse proteins and redirect the signaling to G protein-independent pathways. The functions of free arrestins are poorly understood, and the interaction sites of the non-receptor arrestin partners are largely unknown. In this study, we show that cone arrestin, the least studied member of the family, binds c-Jun N-terminal kinase (JNK3) and Mdm2 and regulates their subcellular distribution. Using arrestin mutants with increased or reduced structural flexibility, we demonstrate that arrestin in all conformations binds JNK3 comparably, whereas Mdm2 preferentially binds cone arrestin ,frozen' in the basal state. To localize the interaction sites, we expressed separate N- and C-domains of cone and rod arrestins and found that individual domains bind JNK3 and remove it from the nucleus as efficiently as full-length proteins. Thus, the arrestin binding site for JNK3 includes elements in both domains with the affinity of partial sites on individual domains sufficient for JNK3 relocalization. N-domain of rod arrestin binds Mdm2, which localizes its main interaction site to this region. Comparable binding of JNK3 and Mdm2 to four arrestin subtypes allowed us to identify conserved residues likely involved in these interactions. [source] Breaking symmetry in protein dimers: Designs and functionsPROTEIN SCIENCE, Issue 1 2006Jerry H. Brown Abstract Symmetry, and in particular point group symmetry, is generally the rule for the global arrangement between subunits in homodimeric and other oligomeric proteins. The structures of fragments of tropomyosin and bovine fibrinogen are recently published examples, however, of asymmetric interactions between chemically identical chains. Their departures from strict twofold symmetry are based on simple and generalizable chemical designs, but were not anticipated prior to their structure determinations. The current review aims to improve our understanding of the structural principles and functional consequences of asymmetric interactions in proteins. Here, a survey of >100 diverse homodimers has focused on the structures immediately adjacent to the twofold axis. Five regular frameworks in ,-helical coiled coils and antiparallel ,-sheets accommodate many of the twofold symmetric axes. On the basis of these frameworks, certain sequence motifs can break symmetry in geometrically defined manners. In antiparallel ,-sheets, these asymmetries include register slips between strands of repeating residues and the adoption of different side-chain rotamers to avoid steric clashes of bulky residues. In parallel coiled coils, an axial stagger between the ,-helices is produced by clusters of core alanines. Such simple designs lead to a basic understanding of the functions of diverse proteins. These functions include regulation of muscle contraction by tropomyosin, blood clot formation by fibrin, half-of-site reactivity of caspase-9, and adaptive protein recognition in the matrix metalloproteinase MMP9. Moreover, asymmetry between chemically identical subunits, by producing multiple equally stable conformations, leads to unique dynamic and self-assembly properties. [source] Caspase activation, inhibition, and reactivation: A mechanistic viewPROTEIN SCIENCE, Issue 8 2004Yigong Shi Abstract Caspases, a unique family of cysteine proteases, execute programmed cell death (apoptosis). Caspases exist as inactive zymogens in cells and undergo a cascade of catalytic activation at the onset of apoptosis. The activated caspases are subject to inhibition by the inhibitor-of-apoptosis (IAP) family of proteins. This inhibition can be effectively removed by diverse proteins that share an IAP-binding tetrapeptide motif. Recent structural and biochemical studies have revealed the underlying molecular mechanisms for these processes in mammals and in Drosophila. This paper reviews these latest advances. [source] Proteomic profiling of tandem affinity purified 14-3-3 protein complexes in Arabidopsis thalianaPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 11 2009Ing-Feng Chang Abstract In eukaryotes, 14-3-3 dimers regulate hundreds of functionally diverse proteins (clients), typically in phosphorylation-dependent interactions. To uncover new clients, 14-3-3 omega (At1g78300) from Arabidopsis was engineered with a "tandem affinity purification" tag and expressed in transgenic plants. Purified complexes were analyzed by tandem MS. Results indicate that 14-3-3 omega can dimerize with at least 10 of the 12 14-3-3 isoforms expressed in Arabidopsis. The identification here of 121 putative clients provides support for in vivo 14-3-3 interactions with a diverse array of proteins, including those involved in: (i) Ion transport, such as a K+ channel (GORK), a Cl, channel (CLCg), Ca2+ channels belonging to the glutamate receptor family (1.2, 2.1, 2.9, 3.4, 3.7); (ii) hormone signaling, such as ACC synthase (isoforms ACS-6, -7 and -8 involved in ethylene synthesis) and the brassinolide receptors BRI1 and BAK1; (iii) transcription, such as 7 WRKY family transcription factors; (iv) metabolism, such as phosphoenol pyruvate carboxylase; and (v) lipid signaling, such as phospholipase D (, and ,). More than 80% (101) of these putative clients represent previously unidentified 14-3-3 interactors. These results raise the number of putative 14-3-3 clients identified in plants to over 300. [source] The structure of DinB from Geobacillus stearothermophilus: a representative of a unique four-helix-bundle superfamilyACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 3 2010David R. Cooper The crystal structure of the dinB gene product from Geobacillus stearothermophilus (GsDinB) is reported at 2.5,Å resolution. The dinB gene is one of the DNA-damage-induced genes and the corresponding protein, DinB, is the founding member of a Pfam family with no known function. The protein contains a four-helix up,down,down,up bundle that has previously been described in the literature in three disparate proteins: the enzyme MDMPI (mycothiol-dependent maleylpyruvate isomerase), YfiT and TTHA0303, a member of a small DUF (domain of unknown function). However, a search of the DALI structural database revealed similarities to a further 11 new unpublished structures contributed by structural genomics centers. The sequences of these proteins are quite divergent and represent several Pfam families, yet their structures are quite similar and most (but not all) seem to have the ability to coordinate a metal ion using a conserved histidine-triad motif. The structural similarities of these diverse proteins suggest that a new Pfam clan encompassing the families that share this fold should be created. The proteins that share this fold exhibit four different quaternary structures: monomeric and three different dimeric forms. [source] | |||||||||||||