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PDBsum entry 3thy
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DNA binding protein/DNA
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PDB id
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3thy
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References listed in PDB file
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Key reference
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Title
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Mechanism of mismatch recognition revealed by human mutsβ bound to unpaired DNA loops.
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Authors
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S.Gupta,
M.Gellert,
W.Yang.
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Ref.
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Nat Struct Biol, 2011,
19,
72-78.
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PubMed id
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Abstract
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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.
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