MUTSd

DNA-binding domain of DNA mismatch repair MUTS family
MUTSd
SMART accession number:SM00533
Description: -
Interpro abstract (IPR007696):

Mismatch repair contributes to the overall fidelity of DNA replication and is essential for combating the adverse effects of damage to the genome. It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase complex. The post-replicative Mismatch Repair System (MMRS) of Escherichia coli involves MutS (Mutator S), MutL and MutH proteins, and acts to correct point mutations or small insertion/deletion loops produced during DNA replication [ (PUBMED:17919654) ]. MutS and MutL are involved in preventing recombination between partially homologous DNA sequences. The assembly of MMRS is initiated by MutS, which recognises and binds to mispaired nucleotides and allows further action of MutL and MutH to eliminate a portion of newly synthesized DNA strand containing the mispaired base [ (PUBMED:17599803) ]. MutS can also collaborate with methyltransferases in the repair of O(6)-methylguanine damage, which would otherwise pair with thymine during replication to create an O(6)mG:T mismatch [ (PUBMED:17951114) ]. MutS exists as a dimer, where the two monomers have different conformations and form a heterodimer at the structural level [ (PUBMED:17426027) ]. Only one monomer recognises the mismatch specifically and has ADP bound. Non-specific major groove DNA-binding domains from both monomers embrace the DNA in a clamp-like structure. Mismatch binding induces ATP uptake and a conformational change in the MutS protein, resulting in a clamp that translocates on DNA.

MutS is a modular protein with a complex structure [ (PUBMED:11048711) ], and is composed of:

  • N-terminal mismatch-recognition domain, which is similar in structure to tRNA endonuclease.
  • Connector domain, which is similar in structure to Holliday junction resolvase ruvC.
  • Core domain, which is composed of two separate subdomains that join together to form a helical bundle; from within the core domain, two helices act as levers that extend towards (but do not touch) the DNA.
  • Clamp domain, which is inserted between the two subdomains of the core domain at the top of the lever helices; the clamp domain has a beta-sheet structure.
  • ATPase domain (connected to the core domain), which has a classical Walker A motif.
  • HTH (helix-turn-helix) domain, which is involved in dimer contacts.

The MutS family of proteins is named after the Salmonella typhimurium MutS protein involved in mismatch repair. Homologues of MutS have been found in many species including eukaryotes (MSH 1, 2, 3, 4, 5, and 6 proteins), archaea and bacteria, and together these proteins have been grouped into the MutS family. Although many of these proteins have similar activities to the E. coli MutS, there is significant diversity of function among the MutS family members. Human MSH has been implicated in non-polyposis colorectal carcinoma (HNPCC) and is a mismatch binding protein [ (PUBMED:8036718) ].This diversity is even seen within species, where many species encode multiple MutS homologues with distinct functions [ (PUBMED:9722651) ]. Inter-species homologues may have arisen through frequent ancient horizontal gene transfer of MutS (and MutL) from bacteria to archaea and eukaryotes via endosymbiotic ancestors of mitochondria and chloroplasts [ (PUBMED:17965091) ].

This entry represents the core domain (domain 3) found in proteins of the MutS family. The core domain of MutS adopts a multi-helical structure comprised of two subdomains, which are interrupted by the clamp domain. Two of the helices in the core domain comprise the levers that extend towards the DNA. This domain is found associated with Pfam:PF00488, Pfam:PF05188, Pfam:PF01624 and Pfam:PF05190. The aligned region corresponds with domain III, which is central to the structure of Thermus aquaticus MutS as characterised in [ (PUBMED:11048710) ].

GO process:mismatch repair (GO:0006298)
GO function:ATP binding (GO:0005524), mismatched DNA binding (GO:0030983)
Family alignment:
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There are 35562 MUTSd domains in 35556 proteins in SMART's nrdb database.

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