2gwf

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{{STRUCTURE_2gwf| PDB=2gwf | SCENE= }}
{{STRUCTURE_2gwf| PDB=2gwf | SCENE= }}
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'''Structure of a USP8-NRDP1 complex'''
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===Structure of a USP8-NRDP1 complex===
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==Overview==
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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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(as it appears on PubMed at http://www.pubmed.gov), where 17035239 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17035239}}
==About this Structure==
==About this Structure==
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[[Category: Structural genomics consortium]]
[[Category: Structural genomics consortium]]
[[Category: Ubl conjugation pathway]]
[[Category: Ubl conjugation pathway]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:37:10 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:05:35 2008''

Revision as of 10:05, 27 July 2008

Image:2gwf.png

Template:STRUCTURE 2gwf

Structure of a USP8-NRDP1 complex

Template:ABSTRACT PUBMED 17035239

About this Structure

2GWF is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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

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