{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":59,"searchCount":0},"additional":{"submitter":["Hargreaves VV"],"funding":["NCI NIH HHS","NIGMS NIH HHS"],"pagination":["41232-44"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3510822"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["287(49)"],"pubmed_abstract":["ATP binding causes the mispair-bound Msh2-Msh6 mismatch recognition complex to slide along the DNA away from the mismatch, and ATP is required for the mispair-dependent interaction between Msh2-Msh6 and Mlh1-Pms1. It has been inferred from these observations that ATP induces conformational changes in Msh2-Msh6; however, the nature of these conformational changes and their requirement in mismatch repair are poorly understood. Here we show that ATP induces a conformational change within the C-terminal region of Msh6 that protects the trypsin cleavage site after Msh6 residue Arg(1124). An engineered disulfide bond within this region prevented the ATP-driven conformational change and resulted in an Msh2-Msh6 complex that bound mispaired bases but could not form sliding clamps or bind Mlh1-Pms1. The engineered disulfide bond also reduced mismatch repair efficiency in vivo, indicating that this ATP-driven conformational change plays a role in mismatch repair."],"journal":["The Journal of biological chemistry"],"pubmed_title":["Engineered disulfide-forming amino acid substitutions interfere with a conformational change in the mismatch recognition complex Msh2-Msh6 required for mismatch repair."],"pmcid":["PMC3510822"],"funding_grant_id":["CA092584","GM50006","R01 GM050006","P01 CA092584"],"pubmed_authors":["Kolodner RD","Hargreaves VV","Putnam CD"],"view_count":["59"],"additional_accession":[]},"is_claimable":false,"name":"Engineered disulfide-forming amino acid substitutions interfere with a conformational change in the mismatch recognition complex Msh2-Msh6 required for mismatch repair.","description":"ATP binding causes the mispair-bound Msh2-Msh6 mismatch recognition complex to slide along the DNA away from the mismatch, and ATP is required for the mispair-dependent interaction between Msh2-Msh6 and Mlh1-Pms1. It has been inferred from these observations that ATP induces conformational changes in Msh2-Msh6; however, the nature of these conformational changes and their requirement in mismatch repair are poorly understood. Here we show that ATP induces a conformational change within the C-terminal region of Msh6 that protects the trypsin cleavage site after Msh6 residue Arg(1124). An engineered disulfide bond within this region prevented the ATP-driven conformational change and resulted in an Msh2-Msh6 complex that bound mispaired bases but could not form sliding clamps or bind Mlh1-Pms1. The engineered disulfide bond also reduced mismatch repair efficiency in vivo, indicating that this ATP-driven conformational change plays a role in mismatch repair.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Nov","modification":"2024-11-15T21:20:43.321Z","creation":"2019-03-27T01:01:16Z"},"accession":"S-EPMC3510822","cross_references":{"pubmed":["23045530"],"doi":["10.1074/jbc.m112.402495","10.1074/jbc.M112.402495"]}}