2fzp

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{{STRUCTURE_2fzp| PDB=2fzp | SCENE= }}
{{STRUCTURE_2fzp| PDB=2fzp | SCENE= }}
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'''Crystal structure of the USP8 interaction domain of human NRDP1'''
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===Crystal structure of the USP8 interaction domain of human NRDP1===
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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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The line below this paragraph, {{ABSTRACT_PUBMED_17035239}}, adds the Publication Abstract to the page
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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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==Reference==
==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:[http://www.ncbi.nlm.nih.gov/pubmed/17035239 17035239]
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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Stabilization of the E3 ubiquitin ligase Nrdp1 by the deubiquitinating enzyme USP8., Wu X, Yen L, Irwin L, Sweeney C, Carraway KL 3rd, Mol Cell Biol. 2004 Sep;24(17):7748-57. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15314180 15314180]
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Nrdp1-mediated degradation of the gigantic IAP, BRUCE, is a novel pathway for triggering apoptosis., Qiu XB, Markant SL, Yuan J, Goldberg AL, EMBO J. 2004 Feb 25;23(4):800-10. Epub 2004 Feb 12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14765125 14765125]
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An RBCC protein implicated in maintenance of steady-state neuregulin receptor levels., Diamonti AJ, Guy PM, Ivanof C, Wong K, Sweeney C, Carraway KL 3rd, Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2866-71. Epub 2002 Feb 26. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11867753 11867753]
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FLRF, a novel evolutionarily conserved RING finger gene, is differentially expressed in mouse fetal and adult hematopoietic stem cells and progenitors., Abdullah JM, Li X, Nachtman RG, Jurecic R, Blood Cells Mol Dis. 2001 Jan-Feb;27(1):320-33. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11358394 11358394]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Structural genomic]]
[[Category: Structural genomic]]
[[Category: Structural genomics consortium]]
[[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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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 03:37:35 2008''

Revision as of 00:37, 29 July 2008

Image:2fzp.png

Template:STRUCTURE 2fzp

Crystal structure of the USP8 interaction domain of human NRDP1

Template:ABSTRACT PUBMED 17035239

About this Structure

2FZP is a Single protein structure of sequence 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

Stabilization of the E3 ubiquitin ligase Nrdp1 by the deubiquitinating enzyme USP8., Wu X, Yen L, Irwin L, Sweeney C, Carraway KL 3rd, Mol Cell Biol. 2004 Sep;24(17):7748-57. PMID:15314180

Nrdp1-mediated degradation of the gigantic IAP, BRUCE, is a novel pathway for triggering apoptosis., Qiu XB, Markant SL, Yuan J, Goldberg AL, EMBO J. 2004 Feb 25;23(4):800-10. Epub 2004 Feb 12. PMID:14765125

An RBCC protein implicated in maintenance of steady-state neuregulin receptor levels., Diamonti AJ, Guy PM, Ivanof C, Wong K, Sweeney C, Carraway KL 3rd, Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2866-71. Epub 2002 Feb 26. PMID:11867753

FLRF, a novel evolutionarily conserved RING finger gene, is differentially expressed in mouse fetal and adult hematopoietic stem cells and progenitors., Abdullah JM, Li X, Nachtman RG, Jurecic R, Blood Cells Mol Dis. 2001 Jan-Feb;27(1):320-33. PMID:11358394

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