2fzp
From Proteopedia
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==Crystal structure of the USP8 interaction domain of human NRDP1== | ==Crystal structure of the USP8 interaction domain of human NRDP1== | ||
| - | <StructureSection load='2fzp' size='340' side='right' caption='[[2fzp]], [[Resolution|resolution]] 1.87Å' scene=''> | + | <StructureSection load='2fzp' size='340' side='right'caption='[[2fzp]], [[Resolution|resolution]] 1.87Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[2fzp]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[2fzp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FZP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FZP FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.87Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2fzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fzp OCA], [https://pdbe.org/2fzp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fzp RCSB], [https://www.ebi.ac.uk/pdbsum/2fzp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fzp ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/RNF41_HUMAN RNF41_HUMAN] Acts as E3 ubiquitin-protein ligase and regulates the degradation of target proteins. Polyubiquitinates MYD88 and Negatively regulates MYD88-dependent production of proinflammatory cytokines but can promote TRIF-dependent production of type I interferon. Promotes also activation of TBK1 and IRF3. Involved in the ubiquitination of erythropoietin (EPO) and interleukin-3 (IL-3) receptors. Thus, through maintaining basal levels of cytokine receptors, RNF41 is involved in the control of hematopoietic progenitor cell differentiation into myeloerythroid lineages (By similarity). Contributes to the maintenance of steady-state ERBB3 levels by mediating its growth factor-independent degradation. Involved in the degradation of the inhibitor of apoptosis BIRC6 and thus is an important regulator of cell death by promoting apoptosis. Acts also as a PARK2 modifier that accelerates its degradation, resulting in a reduction of PARK2 activity, influencing the balance of intracellular redox state.<ref>PMID:12411582</ref> <ref>PMID:14765125</ref> <ref>PMID:15632191</ref> <ref>PMID:17210635</ref> <ref>PMID:18541373</ref> <ref>PMID:19483718</ref> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2fzp ConSurf]. | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2fzp ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Ubiquitin-specific protease 8 (USP8) hydrolyzes mono and polyubiquitylated targets such as epidermal growth factor receptors and is involved in clathrin-mediated internalization. In 1182 residues, USP8 contains multiple domains, including coiled-coil, rhodanese, and catalytic domains. We report the first high-resolution crystal structures of these domains and discuss their implications for USP8 function. The amino-terminal domain is a homodimer with a novel fold. It is composed of two five-helix bundles, where the first helices are swapped, and carboxyl-terminal helices are extended in an antiparallel fashion. The structure of the rhodanese domain, determined in complex with the E3 ligase NRDP1, reveals the canonical rhodanese fold but with a distorted primordial active site. The USP8 recognition domain of NRDP1 has a novel protein fold that interacts with a conserved peptide loop of the rhodanese domain. A consensus sequence of this loop is found in other NRDP1 targets, suggesting a common mode of interaction. The structure of the carboxyl-terminal catalytic domain of USP8 exhibits the conserved tripartite architecture but shows unique traits. Notably, the active site, including the ubiquitin binding pocket, is in a closed conformation, incompatible with substrate binding. The presence of a zinc ribbon subdomain near the ubiquitin binding site further suggests a polyubiquitin-specific binding site and a mechanism for substrate induced conformational changes. | ||
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| - | Amino-terminal dimerization, NRDP1-rhodanese interaction, and inhibited catalytic domain conformation of the ubiquitin-specific protease 8 (USP8).,Avvakumov GV, Walker JR, Xue S, Finerty PJ Jr, Mackenzie F, Newman EM, Dhe-Paganon S J Biol Chem. 2006 Dec 8;281(49):38061-70. Epub 2006 Oct 11. PMID:17035239<ref>PMID:17035239</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 2fzp" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: Arrowsmith | + | [[Category: Large Structures]] |
| - | [[Category: Avvakumov | + | [[Category: Arrowsmith C]] |
| - | [[Category: Bochkarev | + | [[Category: Avvakumov GV]] |
| - | [[Category: Butler-Cole | + | [[Category: Bochkarev A]] |
| - | [[Category: Dhe-Paganon | + | [[Category: Butler-Cole C]] |
| - | [[Category: Edwards | + | [[Category: Dhe-Paganon S]] |
| - | [[Category: Finerty | + | [[Category: Edwards A]] |
| - | [[Category: Newman | + | [[Category: Finerty Jr PJ]] |
| - | + | [[Category: Newman EM]] | |
| - | [[Category: Sundstrom | + | [[Category: Sundstrom M]] |
| - | [[Category: Walker | + | [[Category: Walker JR]] |
| - | [[Category: Weigelt | + | [[Category: Weigelt J]] |
| - | [[Category: Xue | + | [[Category: Xue S]] |
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Current revision
Crystal structure of the USP8 interaction domain of human NRDP1
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Categories: Homo sapiens | Large Structures | Arrowsmith C | Avvakumov GV | Bochkarev A | Butler-Cole C | Dhe-Paganon S | Edwards A | Finerty Jr PJ | Newman EM | Sundstrom M | Walker JR | Weigelt J | Xue S
