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排序方式: 共有290条查询结果,搜索用时 15 毫秒
141.
Cursi S Rufini A Stagni V Condò I Matafora V Bachi A Bonifazi AP Coppola L Superti-Furga G Testi R Barilà D 《The EMBO journal》2006,25(9):1895-1905
We identified Caspase-8 as a new substrate for Src kinase. Phosphorylation occurs on Tyr380, situated in the linker region between the large and the small subunits of human Procaspase-8, and results in downregulation of Caspase-8 proapoptotic function. Src activation triggers Caspase-8 phosphorylation on Tyr380 and impairs Fas-induced apoptosis. Accordingly, Src failed to protect Caspase-8-defective human cells in which a Caspase-8-Y380F mutant is expressed from Fas-induced cell death. Remarkably, Src activation upon EGF-receptor stimulation triggers endogenous Caspase-8 phosphorylation and prevents Fas-induced apoptosis. Tyr380 is phosphorylated also in human colon cancers where Src is aberrantly activated. These data provide the first evidence for a direct role of tyrosine phosphorylation in the control of caspases and reveal a new mechanism through which tyrosine kinases inhibit apoptosis and participate in tumor progression. 相似文献
142.
Claudia Andreini Ivano Bertini Gabriele Cavallaro Rafael J. Najmanovich Janet M. Thornton 《Journal of molecular biology》2009,388(2):356-804
In metalloproteins, the protein environment modulates metal properties to achieve the required goal, which can be protein stabilization or function. The analysis of metal sites at the atomic level of detail provided by protein structures can thus be of benefit in functional and evolutionary studies of proteins. In this work, we propose a structural bioinformatics approach to the study of metalloproteins based on structural templates of metal sites that include the PDB coordinates of protein residues forming the first and the second coordination sphere of the metal. We have applied this approach to non-heme iron sites, which have been analyzed at various levels. Templates of sites located in different protein domains have been compared, showing that similar sites can be found in unrelated proteins as the result of convergent evolution. Templates of sites located in proteins of a large superfamily have been compared, showing possible mechanisms of divergent evolution of proteins to achieve different functions. Furthermore, template comparisons have been used to predict the function of uncharacterized proteins, showing that similarity searches focused on metal sites can be advantageously combined with typical whole-domain comparisons. Structural templates of metal sites, finally, may constitute the basis for a systematic classification of metalloproteins in databases. 相似文献
143.
Lucia Banci Ivano Bertini Simone Ciofi-Baffoni Luisa Poggi Murugendra Vanarotti Stephen Tottey Kevin J. Waldron Nigel J. Robinson 《Journal of biological inorganic chemistry》2010,15(1):87-98
A Cu(I) metallochaperone, Atx1, interacts with the amino-terminal domain of a Cu(I)-transporting ATPase, PacSN, but not with a domain of related Zn-transporting ATPase, ZiaAN in Synechocystis PCC 6803. This is thought to prevent ZiaAN from acquiring Cu(I), which it binds more tightly than Zn. Solution structures of Atx1, PacSN, and the heterodimer were previously described. Here we report solution structural studies of the ZiaAN soluble domain. Apo-ZiaAN has a typical ferredoxin-like fold followed by an atypical 34 residues of unstructured polypeptide containing a His7 motif. ZiaAN competes with the metallochromic indicator 4-(2-pyridylazo)resorcinol for 1 equiv of Zn, which can be displaced by thiol-modifying
p-mercuriphenylsulfonic acid, establishing that a high-affinity site involves thiols of the CXXC motif within the ferredoxin-like
fold. A single equivalent of Zn affects nuclear magnetic resonance signals arising from the CXXC motif as well as all seven
His residues. The presence of NMR-line broadening in both sites implies that Zn1-ZiaAN undergoes exchange phenomena, consistent with CXXC-bound Zn coincidentally sampling various His ligands. These Zn-dependent
dynamic changes could either aid metal transfer or alter intramolecular interactions. No formation of Atx1–Cu(I)–ZiaAN heterodimers was observed, and in the presence of equimolar ZiaAN and PacSN, only Atx1–Cu(I)–PacSN complexes were detected. Residues flanking the CXXC motif of PacSN (R13-ASS20) differ in charge and bulk from those of ZiaAN (D18-KLK25) and make contacts in the Atx1–Cu(I)–PacSN complex. Crucially, swapping these residues flanking the CXXC motifs of ZiaAN and PacSN reciprocally swaps partner choice by Atx1. These few residues of the two ATPases have diverged during evolution to bias Atx1
interactions in favor of PacSN rather than ZiaAN. 相似文献
144.
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147.
Lucia Banci Ivano Bertini Simone Ciofi-Baffoni Tatiana Kozyreva Mirko Mori Shenlin Wang 《Journal of biological inorganic chemistry》2011,16(3):391-403
Sco proteins are widespread in eukaryotic and in many prokaryotic organisms. They have a thioredoxin-like fold and bind a
single copper(I) or copper(II) ion through a CXXXC motif and a conserved His ligand, with both tight and weak affinities.
They have been implicated in the assembly of the CuA site of cytochrome c oxidase as copper chaperones and/or thioredoxins. In this work we have structurally characterized a Sco domain which is naturally
fused with a typical electron transfer molecule, i.e., cytochrome c, in Pseudomonas putida. The thioredoxin-like Sco domain does not bind copper(II), binds copper(I) with weak affinity without involving the conserved
His, and has redox properties consisting of a thioredoxin activity and of the ability of reducing copper(II) to copper(I),
and iron(III) to iron(II) of the cytochrome c domain. These findings indicate that the His ligand coordination is the discriminating factor for introducing a metallochaperone
function in a thioredoxin-like fold, typically responsible for electron transfer processes. A comparative structural analysis
of the Sco domain from P. putida versus eukaryotic Sco proteins revealed structural determinants affecting the formation of a tight-affinity versus a weak-affinity
copper binding site in Sco proteins. 相似文献
148.
This paper is a continuation of our study of the connection between the changing environment and the changing use of particular elements in organisms in the course of their combined evolution (Decaria, Bertini and Williams, Metallomics, 2010, 2, 706). Here we treat the changes in copper proteins in historically the same increasingly oxidising environmental conditions. The study is a bioinformatic analysis of the types and the numbers of copper domains of proteins from 435 DNA sequences of a wide range of organisms available in NCBI, using the method developed by Andreini, Bertini and Rosato in Accounts of Chemical Research 2009, 42, 1471. The copper domains of greatest interest are found predominantly in copper chaperones, homeostatic proteins and redox enzymes mainly used outside the cytoplasm which are in themselves somewhat diverse. The multiplicity of these proteins is strongly marked. The contrasting use of the iron and heme iron proteins in oxidations, mostly in the cytoplasm, is compared with them and with activity of zinc fingers during evolution. It is shown that evolution is a coordinated development of the chemistry of elements with use of novel and multiple copies of their proteins as their availability rises in the environment. 相似文献
149.
Eberini I Sensi C Barbiroli A Bonomi F Iametti S Galliano M Gianazza E 《Amino acids》2012,42(5):2019-2030
We report on electrophoretic, spectroscopic, and computational studies aimed at clarifying, at atomic resolution, the electrostatics
of folded and unfolded bovine β-lactoglobulin (BLG) with a detailed characterization of the specific aminoacids involved.
The procedures we used involved denaturant gradient gel electrophoresis, isoelectric focusing, electrophoretic titration curves,
circular dichroism and fluorescence spectra in the presence of increasing concentrations of urea (up to 8 M), electrostatics
computations and low-mode molecular dynamics. Discrepancy between electrophoretic and spectroscopic evidence suggests that
changes in mobility induced by urea are not just the result of changes in gyration radius upon unfolding. Electrophoretic
titration curves run across a pH range of 3.5–9 in the presence of urea suggest that more than one aminoacid residue may have
anomalous pK
a value in native BLG. Detailed computational studies indicate a shift in pKa of Glu44, Glu89, and Glu114, mainly due to changes in global and local desolvation. For His161, the formation of hydrogen
bond(s) could add up to desolvation contributions. However, since His161 is at the C terminus, the end-effect associated to
the solvated form strongly influences its pK
a value with extreme variation between crystal structures on one side and NMR or low-mode molecular dynamics structures on
the other. The urea concentration effective in BLG unfolding depends on pH, with higher stability of the protein at lower
pH. 相似文献
150.
Zumsteg A Luster J Göransson H Smittenberg RH Brunner I Bernasconi SM Zeyer J Frey B 《Microbial ecology》2012,63(3):552-564
Glacier forefield chronosequences, initially composed of barren substrate after glacier retreat, are ideal locations to study
primary microbial colonization and succession in a natural environment. We characterized the structure and composition of
bacterial, archaeal and fungal communities in exposed rock substrates along the Damma glacier forefield in central Switzerland.
Soil samples were taken along the forefield from sites ranging from fine granite sand devoid of vegetation near the glacier
terminus to well-developed soils covered with vegetation. The microbial communities were studied with genetic profiling (T-RFLP)
and sequencing of clone libraries. According to the T-RFLP profiles, bacteria showed a high Shannon diversity index (H) (ranging from 2.3 to 3.4) with no trend along the forefield. The major bacterial lineages were Proteobacteria, Actinobacteria, Acidobacteria, Firmicutes and Cyanobacteria. An interesting finding was that Euryarchaeota were predominantly colonizing young soils and Crenarchaeota mainly mature soils. Fungi shifted from an Ascomycota-dominated community in young soils to a more Basidiomycota-dominated community in old soils. Redundancy analysis indicated that base saturation, pH, soil C and N contents and plant
coverage, all related to soil age, correlated with the microbial succession along the forefield. 相似文献