3THW

Human MutSbeta complexed with an IDL of 4 bases (Loop4) and ADP

Summary for 3THW

• Entry DOI: 10.2210/pdb3thw/pdb
• Related: 3THX 3THY 3THZ
• Descriptor: DNA mismatch repair protein Msh2, DNA mismatch repair protein Msh3, DNA Loop4 hairpin, ... (5 entities in total)
• Functional Keywords: abc family atpase, mismatch recognition, mismatched unpaired idl dna, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : P43246
• Total number of polymer chains: 3
• Total formula weight: 225906.22

Authors

Yang, W. (deposition date: 2011-08-19, release date: 2011-12-21, Last modification date: 2023-09-13)

Primary citation

Gupta, S.,Gellert, M.,Yang, W.
Mechanism of mismatch recognition revealed by human MutSbeta bound to unpaired DNA loops
Nat.Struct.Mol.Biol., 19:72-78, 2012

PubMed Abstract: DNA mismatch repair corrects replication errors, thus reducing mutation rates and microsatellite instability. Genetic defects in this pathway cause Lynch syndrome and various cancers in humans. Binding of a mispaired or unpaired base by bacterial MutS and eukaryotic MutSα is well characterized. We report here crystal structures of human MutSβ in complex with DNA containing insertion-deletion loops (IDL) of two, three, four or six unpaired nucleotides. In contrast to eukaryotic MutSα and bacterial MutS, which bind the base of a mismatched nucleotide, MutSβ binds three phosphates in an IDL. DNA is severely bent at the IDL; unpaired bases are flipped out into the major groove and partially exposed to solvent. A normal downstream base pair can become unpaired; a single unpaired base can thereby be converted to an IDL of two nucleotides and recognized by MutSβ. The C-terminal dimerization domains form an integral part of the MutS structure and coordinate asymmetrical ATP hydrolysis by Msh2 and Msh3 with mismatch binding to signal for repair.

PubMed: 22179786
DOI: 10.1038/nsmb.2175

Experimental method

X-RAY DIFFRACTION (3.09 Å)