Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA

Nature. 2000 Oct 12;407(6805):703-10. doi: 10.1038/35037509.


DNA mismatch repair is critical for increasing replication fidelity in organisms ranging from bacteria to humans. MutS protein, a member of the ABC ATPase superfamily, recognizes mispaired and unpaired bases in duplex DNA and initiates mismatch repair. Mutations in human MutS genes cause a predisposition to hereditary nonpolyposis colorectal cancer as well as sporadic tumours. Here we report the crystal structures of a MutS protein and a complex of MutS with a heteroduplex DNA containing an unpaired base. The structures reveal the general architecture of members of the MutS family, an induced-fit mechanism of recognition between four domains of a MutS dimer and a heteroduplex kinked at the mismatch, a composite ATPase active site composed of residues from both MutS subunits, and a transmitter region connecting the mismatch-binding and ATPase domains. The crystal structures also provide a molecular framework for understanding hereditary nonpolyposis colorectal cancer mutations and for postulating testable roles of MutS.

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Base Pair Mismatch*
  • Binding Sites
  • Crystallography, X-Ray
  • DNA Repair*
  • DNA, Bacterial / chemistry*
  • DNA, Bacterial / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Escherichia coli Proteins*
  • Macromolecular Substances
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • MutS DNA Mismatch-Binding Protein
  • Nucleic Acid Conformation
  • Nucleic Acid Heteroduplexes
  • Protein Binding
  • Protein Conformation
  • Thermus / genetics


  • Bacterial Proteins
  • DNA, Bacterial
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • Macromolecular Substances
  • Nucleic Acid Heteroduplexes
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • MutS DNA Mismatch-Binding Protein
  • MutS protein, E coli

Associated data

  • PDB/1EWQ
  • PDB/1EWR