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2nvu

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[[Image:2nvu.gif|left|200px]]
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{{STRUCTURE_2nvu| PDB=2nvu | SCENE= }}
{{STRUCTURE_2nvu| PDB=2nvu | SCENE= }}
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'''Structure of APPBP1-UBA3~NEDD8-NEDD8-MgATP-Ubc12(C111A), a trapped ubiquitin-like protein activation complex'''
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===Structure of APPBP1-UBA3~NEDD8-NEDD8-MgATP-Ubc12(C111A), a trapped ubiquitin-like protein activation complex===
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==Overview==
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Ubiquitin-like proteins (UBLs) are conjugated by dynamic E1-E2-E3 enzyme cascades. E1 enzymes activate UBLs by catalysing UBL carboxy-terminal adenylation, forming a covalent E1 throught UBL thioester intermediate, and generating a thioester-linked E2 throught UBL product, which must be released for subsequent reactions. Here we report the structural analysis of a trapped UBL activation complex for the human NEDD8 pathway, containing NEDD8's heterodimeric E1 (APPBP1-UBA3), two NEDD8s (one thioester-linked to E1, one noncovalently associated for adenylation), a catalytically inactive E2 (Ubc12), and MgATP. The results suggest that a thioester switch toggles E1-E2 affinities. Two E2 binding sites depend on NEDD8 being thioester-linked to E1. One is unmasked by a striking E1 conformational change. The other comes directly from the thioester-bound NEDD8. After NEDD8 transfer to E2, reversion to an alternate E1 conformation would facilitate release of the E2 throught NEDD8 thioester product. Thus, transferring the UBL's thioester linkage between successive conjugation enzymes can induce conformational changes and alter interaction networks to drive consecutive steps in UBL cascades.
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(as it appears on PubMed at http://www.pubmed.gov), where 17220875 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17220875}}
==About this Structure==
==About this Structure==
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[[Category: Thioester]]
[[Category: Thioester]]
[[Category: Ubiquitin]]
[[Category: Ubiquitin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:58:05 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:31:07 2008''

Revision as of 11:31, 28 July 2008

Image:2nvu.png

Template:STRUCTURE 2nvu

Structure of APPBP1-UBA3~NEDD8-NEDD8-MgATP-Ubc12(C111A), a trapped ubiquitin-like protein activation complex

Template:ABSTRACT PUBMED 17220875

About this Structure

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

Reference

Basis for a ubiquitin-like protein thioester switch toggling E1-E2 affinity., Huang DT, Hunt HW, Zhuang M, Ohi MD, Holton JM, Schulman BA, Nature. 2007 Jan 25;445(7126):394-8. Epub 2007 Jan 14. PMID:17220875

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