Summary information and primary citation

PDB-id
3thy; SNAP-derived features in text and JSON formats; DNAproDB
Class
DNA binding protein-DNA
Method
X-ray (2.894 Å)
Summary
Human mutsbeta complexed with an idl of 2 bases (loop2) and adp
Reference
Gupta S, Gellert M, Yang W (2012): "Mechanism of mismatch repair revealed by human MutSbeta bound to unpaired DNA loops." Nat.Struct.Mol.Biol., 19, 72-78. doi: 10.1038/nsmb.2175.
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.

Cartoon-block schematics in six views (download the tarball)

PyMOL session file Download PDB file View in 3Dmol.js