4E4W

Structure of the C-terminal domain of the Saccharomyces cerevisiae MUTL alpha (MLH1/PMS1) heterodimer

4E4W の概要

• エントリーDOI: 10.2210/pdb4e4w/pdb
• 関連するPDBエントリー: 4FMN 4FMO
• 分子名称: DNA mismatch repair protein MLH1, DNA mismatch repair protein PMS1, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: mismatch repair, mutl, endonuclease, zn-binding protein, dna damage, dna repair, hydrolase
• 由来する生物種: Saccharomyces cerevisiae S288c (Baker's yeast); 詳細
• 細胞内の位置: Nucleus: P38920 P14242
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61648.41

構造登録者

Gueneau, E.,Legrand, P.,Charbonnier, J.B. (登録日: 2012-03-13, 公開日: 2013-02-20, 最終更新日: 2024-02-28)

主引用文献

Gueneau, E.,Dherin, C.,Legrand, P.,Tellier-Lebegue, C.,Gilquin, B.,Bonnesoeur, P.,Londino, F.,Quemener, C.,Le Du, M.H.,Marquez, J.A.,Moutiez, M.,Gondry, M.,Boiteux, S.,Charbonnier, J.B.
Structure of the MutLalpha C-terminal domain reveals how Mlh1 contributes to Pms1 endonuclease site.
Nat.Struct.Mol.Biol., 20:461-468, 2013

PubMed Abstract: Mismatch-repair factors have a prominent role in surveying eukaryotic DNA-replication fidelity and in ensuring correct meiotic recombination. These functions depend on MutL-homolog heterodimers with Mlh1. In humans, MLH1 mutations underlie half of hereditary nonpolyposis colorectal cancers (HNPCCs). Here we report crystal structures of the MutLα (Mlh1-Pms1 heterodimer) C-terminal domain (CTD) from Saccharomyces cerevisiae, alone and in complex with fragments derived from Mlh1 partners. These structures reveal structural rearrangements and additional domains in MutLα as compared to the bacterial MutL counterparts and show that the strictly conserved C terminus of Mlh1 forms part of the Pms1 endonuclease site. The structures of the ternary complexes between MutLα(CTD) and Exo1 or Ntg2 fragments reveal the binding mode of the MIP-box motif shared by several Mlh1 partners. Finally, the structures provide a rationale for the deleterious impact of MLH1 mutations in HNPCCs.

PubMed: 23435383
DOI: 10.1038/nsmb.2511

実験手法

X-RAY DIFFRACTION (2.5 Å)