Document Detail

Structural basis for the recognition of N-end rule substrates by the UBR box of ubiquitin ligases.
MedLine Citation:
PMID:  20835240     Owner:  NLM     Status:  In-Process    
The N-end rule pathway is a regulated proteolytic system that targets proteins containing destabilizing N-terminal residues (N-degrons) for ubiquitination and proteasomal degradation in eukaryotes. The N-degrons of type 1 substrates contain an N-terminal basic residue that is recognized by the UBR box domain of the E3 ubiquitin ligase UBR1. We describe structures of the UBR box of Saccharomyces cerevisiae UBR1 alone and in complex with N-degron peptides, including that of the cohesin subunit Scc1, which is cleaved and targeted for degradation at the metaphase-anaphase transition. The structures reveal a previously unknown protein fold that is stabilized by a novel binuclear zinc center. N-terminal arginine, lysine or histidine side chains of the N-degron are coordinated in a multispecific binding pocket. Unexpectedly, the structures together with our in vitro biochemical and in vivo pulse-chase analyses reveal a previously unknown modulation of binding specificity by the residue at position 2 of the N-degron.
Woo Suk Choi; Byung-Cheon Jeong; Yoo Jin Joo; Myeong-Ryeol Lee; Joon Kim; Michael J Eck; Hyun Kyu Song
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-12
Journal Detail:
Title:  Nature structural & molecular biology     Volume:  17     ISSN:  1545-9985     ISO Abbreviation:  Nat. Struct. Mol. Biol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101186374     Medline TA:  Nat Struct Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1175-81     Citation Subset:  IM    
School of Life Sciences and Biotechnology, Korea University, Anam-Dong, Korea.
Data Bank Information
Bank Name/Acc. No.:
PDB/3NIH;  3NII;  3NIJ;  3NIK;  3NIL;  3NIM;  3NIN;  3NIS;  3NIT
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MeSH Terms
Comment In:
Nat Struct Mol Biol. 2010 Oct;17(10):1164-5   [PMID:  20924402 ]

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