4FMN

Structure of the C-terminal domain of the Saccharomyces cerevisiae MUTL alpha (MLH1/PMS1) heterodimer bound to a fragment of NTG2

Summary for 4FMN

• Entry DOI: 10.2210/pdb4fmn/pdb
• Related: 4E4W 4FMO
• Descriptor: DNA mismatch repair protein MLH1, DNA mismatch repair protein PMS1, DNA repair peptide, ... (7 entities in total)
• Functional Keywords: mismatch repair, mutl, endonuclease, zn-binding protein, dna damage, dna repair, hydrolase
• Biological source: Saccharomyces cerevisiae (yeast); More
• Cellular location: Nucleus: P38920 P14242 Q08214
• Total number of polymer chains: 3
• Total formula weight: 63236.33

Authors

Gueneau, E.,Legrand, P.,Charbonnier, J.B. (deposition date: 2012-06-18, release date: 2013-02-20, Last modification date: 2024-11-27)

Primary citation

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 MutL alpha 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

Experimental method

X-RAY DIFFRACTION (2.69 Å)