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Large conformational changes in MutS during DNA scanning, mismatch recognition and repair signalling
Author(s) -
Qiu Ruoyi,
DeRocco Vanessa C,
Harris Credle,
Sharma Anushi,
Hingorani Manju M,
Erie Dorothy A,
Weninger Keith R
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.95
Subject(s) - biology , dna mismatch repair , dna , signalling , dna repair , microbiology and biotechnology , genetics , dna binding protein , computational biology , gene , transcription factor
MutS protein recognizes mispaired bases in DNA and targets them for mismatch repair. Little is known about the transient conformations of MutS as it signals initiation of repair. We have used single‐molecule fluorescence resonance energy transfer (FRET) measurements to report the conformational dynamics of MutS during this process. We find that the DNA‐binding domains of MutS dynamically interconvert among multiple conformations when the protein is free and while it scans homoduplex DNA. Mismatch recognition restricts MutS conformation to a single state. Steady‐state measurements in the presence of nucleotides suggest that both ATP and ADP must be bound to MutS during its conversion to a sliding clamp form that signals repair. The transition from mismatch recognition to the sliding clamp occurs via two sequential conformational changes. These intermediate conformations of the MutS:DNA complex persist for seconds, providing ample opportunity for interaction with downstream proteins required for repair.