2fzp

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[[Image:2fzp.gif|left|200px]]
 
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==Crystal structure of the USP8 interaction domain of human NRDP1==
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The line below this paragraph, containing "STRUCTURE_2fzp", creates the "Structure Box" on the page.
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<StructureSection load='2fzp' size='340' side='right'caption='[[2fzp]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.87&#8491;</td></tr>
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<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>
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{{STRUCTURE_2fzp| PDB=2fzp | SCENE= }}
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</table>
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== Function ==
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'''Crystal structure of the USP8 interaction domain of human NRDP1'''
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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==Overview==
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Check<jmol>
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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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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fz/2fzp_consurf.spt"</scriptWhenChecked>
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==About this Structure==
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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2FZP is a [[Single protein]] structure of sequence from [http://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].
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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==Reference==
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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].
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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:[http://www.ncbi.nlm.nih.gov/pubmed/17035239 17035239]
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Arrowsmith, C.]]
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[[Category: Arrowsmith C]]
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[[Category: Avvakumov, G V.]]
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[[Category: Avvakumov GV]]
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[[Category: Bochkarev, A.]]
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[[Category: Bochkarev A]]
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[[Category: Butler-Cole, C.]]
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[[Category: Butler-Cole C]]
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[[Category: Dhe-Paganon, S.]]
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[[Category: Dhe-Paganon S]]
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[[Category: Edwards, A.]]
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[[Category: Edwards A]]
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[[Category: Jr., P J.Finerty.]]
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[[Category: Finerty Jr PJ]]
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[[Category: Newman, E M.]]
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[[Category: Newman EM]]
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[[Category: SGC, Structural Genomics Consortium.]]
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[[Category: Sundstrom M]]
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[[Category: Sundstrom, M.]]
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[[Category: Walker JR]]
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[[Category: Walker, J R.]]
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[[Category: Weigelt J]]
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[[Category: Weigelt, J.]]
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[[Category: Xue S]]
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[[Category: Xue, S.]]
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[[Category: E3 ligase]]
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[[Category: Protein ubiquitination]]
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[[Category: Sgc]]
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[[Category: Structural genomic]]
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[[Category: Structural genomics consortium]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:30:46 2008''
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Current revision

Crystal structure of the USP8 interaction domain of human NRDP1

PDB ID 2fzp

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