Open AccessA conserved MutS homolog connector domain interface interacts with MutL homologs
Author(s) -
Marc L. Mendillo,
Victoria V. Hargreaves,
Jonathan W. Jamison,
Ashley O. Mo,
Sheng Li,
Christopher D. Putnam,
Virgil L. Woods,
Richard D. Kolodner
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0912250106
Subject(s) - dna mismatch repair , msh2 , msh6 , mlh1 , chemistry , ternary complex , thermus thermophilus , biology , microbiology and biotechnology , escherichia coli , dna , dna repair , biochemistry , gene , enzyme
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.