title: Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome.
abstract: Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson-Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot's syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.
authors.affiliation: Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada.
authors.forename: Hong
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Lam
authors.affiliation: Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Tempel
authors.affiliation: Myriad Genetic Laboratories Inc., 320 Wakara Way, Salt Lake City, UT 84108, USA.
authors.forename: Iain D
authors.initials: ID
authors.lastname: Kerr
authors.affiliation: Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Min
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics; D020816:Amino Acid Motifs; D003001:Cloning, Molecular; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D003460:Crystallization; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics; D040681:Structural Homology, Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D000070957:MutL Protein Homolog 1
keywords: ATPase; GHKL; Lynch syndrome; mismatch repair