期刊
MOLECULAR CELL
卷 32, 期 3, 页码 406-414出版社
CELL PRESS
DOI: 10.1016/j.molcel.2008.08.032
关键词
-
资金
- HHMI
- NIH [Al-16892]
- National Science Foundation
- Howard Hughes Medical Institute
- NIH-NCRR [RR-15301]
- DOE Office of Basic Energy Sciences [DF-AC0206CH11357]
The Wend rule targets specific proteins for destruction in prokaryotes and eukaryotes. Here, we report a crystal structure of a bacterial N-end rule adaptor, ClpS, bound to a peptide mimic of an Wend rule substrate. This structure, which was solved at a resolution of 1.15 angstrom, reveals specific recognition of the peptide alpha-amino group via hydrogen bonding and shows that the peptide's N-terminal tyrosine side chain is buried in a deep hydrophobic cleft that preexists on the surface of ClpS. The adaptor side chains that contact the peptide's N-temninal residue are highly conserved in orthologs and in E3 ubiquitin ligases that mediate eukaryotic N-end rule recognition. We show that mutation of critical ClpS contact residues abrogates substrate delivery to and degradation by the AAA+ protease CIpAP, demonstrate that modification of the hydrophobic pocket results in altered Wend rule specificity, and discuss functional implications for the mechanism of substrate delivery.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据