A conserved MutS homolog connector domain interface interacts with MutL homologs

被引：64

作者：

Mendillo, Marc L. ^{[2
]}

Hargreaves, Victoria V. ^{[2
]}

Jamison, Jonathan W. ^{[1
]}

Mo, Ashley O. ^{[1
]}

Li, Sheng ^{[1
]}

Putnam, Christopher D. ^{[1
,2
]}

Woods, Virgil L., Jr. ^{[1
]}

Kolodner, Richard D. ^{[1
,2
,3
,4
]}

机构：

[1] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Sch Med, Ctr Canc, La Jolla, CA 92093 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 52期

基金：

美国国家卫生研究院;

关键词：

deuterium exchange; mass spectrometry; mismatch repair; Mlh1-Pms1; Msh2-Msh6; DNA MISMATCH REPAIR; SACCHAROMYCES-CEREVISIAE MSH2-MSH6; EXCHANGE MASS-SPECTROMETRY; ESCHERICHIA-COLI MUTS; DOMINANT MUTATIONS; PROTEIN COMPLEXES; CRYSTAL-STRUCTURE; ATP HYDROLYSIS; GENE-PRODUCT; BINDING;

D O I：

10.1073/pnas.0912250106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Escherichia coli MutS forms a mispair-dependent ternary complex with MutL that is essential for initiating mismatch repair (MMR) but is structurally uncharacterized, in part owing to its dynamic nature. Here, we used hydrogen/deuterium exchange mass spectrometry and other methods to identify a region in the connector domain (domain II) of MutS that binds MutL and is required for mispair-dependent ternary complex formation and MMR. A structurally conserved region in Msh2, the eukaryotic homolog, was required for formation of a mispair-dependent Msh2-Msh6-Mlh1-Pms1 ternary complex. These data indicate that the connector domain of MutS and Msh2 contains the interface for binding MutL and Mlh1-Pms1, respectively, and support a mechanism whereby mispair and ATP binding induces a conformational change that allows the MutS and Msh2 interfaces to interact with their partners.

引用

页码：22223 / 22228

页数：6

共 52 条

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