A conserved MutS homolog connector domain interface interacts with MutL homologs

Marc L. Mendillo; Victoria V. Hargreaves; Jonathan W. Jamison; Ashley O. Mo; Sheng Li; Christopher D. Putnam; Virgil L. Woods; Richard D. Kolodner

doi:10.1073/pnas.0912250106

A conserved MutS homolog connector domain interface interacts with MutL homologs

Marc L. Mendillo, Victoria V. Hargreaves, Jonathan W. Jamison, Ashley O. Mo, Sheng Li, Christopher D. Putnam, Virgil L. Woods, Richard D. Kolodner

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	22223-22228
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	106
Issue number	52
DOIs	https://doi.org/10.1073/pnas.0912250106
State	Published - Dec 19 2009

Keywords

Deuterium exchange
Mass spectrometry
Mismatch repair
Mlh1-Pms1
Msh2-Msh6

ASJC Scopus subject areas

General

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Mendillo, Marc L. ; Hargreaves, Victoria V. ; Jamison, Jonathan W. ; Mo, Ashley O. ; Li, Sheng ; Putnam, Christopher D. ; Woods, Virgil L. ; Kolodner, Richard D. / A conserved MutS homolog connector domain interface interacts with MutL homologs. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 52. pp. 22223-22228.

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abstract = "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.",

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A conserved MutS homolog connector domain interface interacts with MutL homologs. / Mendillo, Marc L.; Hargreaves, Victoria V.; Jamison, Jonathan W.; Mo, Ashley O.; Li, Sheng; Putnam, Christopher D.; Woods, Virgil L.; Kolodner, Richard D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 52, 19.12.2009, p. 22223-22228.

Research output: Contribution to journal › Article › peer-review

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AU - Li, Sheng

AU - Putnam, Christopher D.

AU - Woods, Virgil L.

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