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

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


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 languageEnglish (US)
Pages (from-to)22223-22228
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number52
StatePublished - Dec 19 2009


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

ASJC Scopus subject areas

  • General

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