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Mendillo, ML, Hargreaves, VV, Jamison, JW, Mo, AO, Li, S, Putnam, CD, Woods, VL Jr and Kolodner, RD (2009) A conserved MutS homolog connector domain interface interacts with MutL homologs. Proc. Natl. Acad. Sci. U.S.A. 106:22223-8


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.


PubMed PMC2796910 Online version:10.1073/pnas.0912250106


Adenosine Triphosphatases/chemistry; Adenosine Triphosphatases/genetics; Adenosine Triphosphatases/metabolism; Adenosine Triphosphate/metabolism; Amino Acid Substitution; DNA Mismatch Repair; DNA, Bacterial/chemistry; DNA, Bacterial/genetics; DNA, Bacterial/metabolism; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Mannose-Binding Lectin/chemistry; Mannose-Binding Lectin/genetics; Mannose-Binding Lectin/metabolism; Models, Molecular; MutS DNA Mismatch-Binding Protein/chemistry; MutS DNA Mismatch-Binding Protein/genetics; MutS DNA Mismatch-Binding Protein/metabolism; Mutagenesis, Site-Directed; Protein Conformation; Protein Interaction Domains and Motifs; Recombinant Fusion Proteins/chemistry; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Solvents


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