Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome
- University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada)
The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. 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.
- OSTI ID:
- 22389087
- Journal Information:
- Acta crystallographica. Section F, Structural biology communications, Vol. 71, Issue Pt 8; Other Information: PMCID: PMC4528928; PMID: 26249686; PUBLISHER-ID: hv5298; PUBLISHER-ID: S2053230X15010183; OAI: oai:pubmedcentral.nih.gov:4528928; Copyright (c) Wu et al. 2015; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA); ISSN 2053-230X
- Country of Publication:
- United States
- Language:
- English
Functional analysis of rare variants in mismatch repair proteins augments results from computation-based predictive methods
|
journal | May 2017 |
Computational and cellular studies reveal structural destabilization and degradation of MLH1 variants in Lynch syndrome
|
posted_content | October 2019 |
Computational and cellular studies reveal structural destabilization and degradation of MLH1 variants in Lynch syndrome
|
journal | November 2019 |
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