Crystal structure and biochemical analysis of the MutS dot ADP dot beryllium fluoride complex suggests a conserved mechanism for ATP interactions in mismatch repair

Alani, Eric, Lee, Jae Young, Schofield, Mark J., Kijas, Amanda W., Hsieh, Peggy and Yang, Wei (2003) Crystal structure and biochemical analysis of the MutS dot ADP dot beryllium fluoride complex suggests a conserved mechanism for ATP interactions in mismatch repair. Journal of Biological Chemistry, 278 18: 16088-16094. doi:10.1074/jbc.M213193200

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Author Alani, Eric
Lee, Jae Young
Schofield, Mark J.
Kijas, Amanda W.
Hsieh, Peggy
Yang, Wei
Title Crystal structure and biochemical analysis of the MutS dot ADP dot beryllium fluoride complex suggests a conserved mechanism for ATP interactions in mismatch repair
Formatted title
Crystal structure and biochemical analysis of the MutS·ADP·beryllium fluoride complex suggests a conserved mechanism for ATP interactions in mismatch repair
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2003-05-02
Sub-type Article (original research)
DOI 10.1074/jbc.M213193200
Open Access Status File (Publisher version)
Volume 278
Issue 18
Start page 16088
End page 16094
Total pages 7
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Formatted abstract
During mismatch repair ATP binding and hydrolysis activities by the MutS family proteins are important for both mismatch recognition and for transducing mismatch recognition signals to downstream repair factors. Despite intensive efforts, a MutS·ATP·DNA complex has eluded crystallographic analysis. Searching for ATP analogs that strongly bound to Thermus aquaticus (Taq) MutS, we found that ADP·beryllium fluoride (ABF), acted as a strong inhibitor of several MutS family ATPases. Furthermore, ABF promoted the formation of a ternary complex containing the Saccharomyces cerevisiae MSH2·MSH6 and MLH1·PMS1 proteins bound to mismatch DNA but did not promote dissociation of MSH2·MSH6 from mismatch DNA. Crystallographic analysis of the Taq MutS·DNA·ABF complex indicated that although this complex was very similar to that of MutS·DNA·ADP, both ADP·Mg2+ moieties in the MutS· DNA·ADP structure were replaced by ABF. Furthermore, a disordered region near the ATP-binding pocket in the MutS B subunit became traceable, whereas the equivalent region in the A subunit that interacts with the mismatched nucleotide remained disordered. Finally, the DNA binding domains of MutS together with the mismatched DNA were shifted upon binding of ABF. We hypothesize that the presence of ABF is communicated between the two MutS subunits through the contact between the ordered loop and Domain III in addition to the intra-subunit helical lever arm that links the ATPase and DNA binding domains.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Centre for Clinical Research Publications
 
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Created: Tue, 17 Jun 2014, 21:50:25 EST by Amanda W. Kijas on behalf of UQ Centre for Clinical Research