title: A conserved MutS homolog connector domain interface interacts with MutL homologs.
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.
authors.affiliation: Ludwig Institute for Cancer Research, University of California, San Diego School of Medicine, La Jolla, CA 92093-0669, USA.
authors.forename: Marc L
authors.initials: ML
authors.lastname: Mendillo
authors.forename: Victoria V
authors.initials: VV
authors.lastname: Hargreaves
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Jamison
authors.forename: Ashley O
authors.initials: AO
authors.lastname: Mo
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Putnam
authors.forename: Virgil L
authors.initials: VL
authors.lastname: Woods
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kolodner
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D019943:Amino Acid Substitution; D053843:DNA Mismatch Repair; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D037601:Mannose-Binding Lectin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012997:Solvents
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D037601:Mannose-Binding Lectin; C074770:MutL protein, E coli; D011993:Recombinant Fusion Proteins; D012997:Solvents; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein; C497175:MutS protein, E coli