PDBsum entry 3thy

DNA binding protein/DNA

PDB id: 3thy

Contents

Protein chains

883 a.a.

857 a.a.

DNA/RNA

Ligands

ADP

Waters ×15

PDB id:

3thy

Name:

DNA binding protein/DNA

Title:

Human mutsbeta complexed with an idl of 2 bases (loop2) and adp

Structure:

DNA mismatch repair protein msh2. Chain: a. Synonym: hmsh2, muts protein homolog 2. Engineered: yes. DNA mismatch repair protein msh3. Chain: b. Fragment: unp residues 219- 1134. Synonym: hmsh3, divergent upstream protein, dup, mismatch repair protein 1, mrp1.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: msh2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: hi5. Gene: duc1, dug, msh3. Synthetic: yes.

Resolution:

2.89Å R-factor: 0.197 R-free: 0.274

Authors:

W.Yang

Key ref:

S.Gupta et al. (2011). Mechanism of mismatch recognition revealed by human MutSβ bound to unpaired DNA loops. Nat Struct Biol, 19, 72-78. PubMed id: 22179786

Date:

19-Aug-11 Release date: 21-Dec-11

Protein chain

P43246  (MSH2_HUMAN) -  DNA mismatch repair protein Msh2 from Homo sapiens

Seq: 934 a.a.

Struc: 883 a.a.

Protein chain

P20585  (MSH3_HUMAN) -  DNA mismatch repair protein Msh3 from Homo sapiens

Seq: 1137 a.a.

Struc: 857 a.a.

DNA/RNA chains

T-C-T-A-T-C-T-G-A-A-G-C-C-G-A-T-C-G-A-T-G 21 bases

T-C-A-T-C-G-A-T-C-G-C-A-G-C-T-T-C-A-G-A-T-A-G-G 24 bases

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

Nat Struct Biol 19:72-78 (2011)

PubMed id: 22179786

Mechanism of mismatch recognition revealed by human MutSβ bound to unpaired DNA loops.

S.Gupta, M.Gellert, W.Yang.

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.