6SNS

DNA mismatch repair proteins MLH1 and MLH3

6SNS の概要

• エントリーDOI: 10.2210/pdb6sns/pdb
• 分子名称: DNA mismatch repair protein MLH1, DNA mismatch repair protein MLH3, ZINC ION, ... (4 entities in total)
• 機能のキーワード: resolvase, mmr, dna repair, meiosis, recombination
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58596.87

構造登録者

Dai, J.,Chervy, P.,Legrand, P.,Ropars, V.,Charbonnier, J.B. (登録日: 2019-08-27, 公開日: 2021-05-19, 最終更新日: 2024-01-24)

主引用文献

Dai, J.,Sanchez, A.,Adam, C.,Ranjha, L.,Reginato, G.,Chervy, P.,Tellier-Lebegue, C.,Andreani, J.,Guerois, R.,Ropars, V.,Le Du, M.H.,Maloisel, L.,Martini, E.,Legrand, P.,Thureau, A.,Cejka, P.,Borde, V.,Charbonnier, J.B.
Molecular basis of the dual role of the Mlh1-Mlh3 endonuclease in MMR and in meiotic crossover formation.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: In budding yeast, the MutL homolog heterodimer Mlh1-Mlh3 (MutLγ) plays a central role in the formation of meiotic crossovers. It is also involved in the repair of a subset of mismatches besides the main mismatch repair (MMR) endonuclease Mlh1-Pms1 (MutLα). The heterodimer interface and endonuclease sites of MutLγ and MutLα are located in their C-terminal domain (CTD). The molecular basis of MutLγ's dual roles in MMR and meiosis is not known. To better understand the specificity of MutLγ, we characterized the crystal structure of MutLγ(CTD). Although MutLγ(CTD) presents overall similarities with MutLα(CTD), it harbors some rearrangement of the surface surrounding the active site, which indicates altered substrate preference. The last amino acids of Mlh1 participate in the Mlh3 endonuclease site as previously reported for Pms1. We characterized alleles and showed a critical role of this Mlh1 extreme C terminus both in MMR and in meiotic recombination. We showed that the MutLγ(CTD) preferentially binds Holliday junctions, contrary to MutLα(CTD). We characterized Mlh3 positions on the N-terminal domain (NTD) and CTD that could contribute to the positioning of the NTD close to the CTD in the context of the full-length MutLγ. Finally, crystal packing revealed an assembly of MutLγ(CTD) molecules in filament structures. Mutation at the corresponding interfaces reduced crossover formation, suggesting that these superstructures may contribute to the oligomer formation proposed for MutLγ. This study defines clear divergent features between the MutL homologs and identifies, at the molecular level, their specialization toward MMR or meiotic recombination functions.

PubMed: 34088835
DOI: 10.1073/pnas.2022704118

実験手法

X-RAY DIFFRACTION (2.6 Å)