Structural basis of the regulation of the CbpA Co-chaperone by its specific modulator CbpM

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DOIResolve DOI: http://doi.org/10.1016/j.jmb.2010.03.006
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TypeArticle
Journal titleJournal of molecular biology
Volume398
Issue1
Pages111121; # of pages: 11
SubjectCbpA-J domain; CbpM; NMRstructure; Site-directedmutagenesis; SPR
AbstractCbpA, one of the Escherichia coli DnaJ homologues, acts as a co-chaperone in the DnaK chaperone system. Despite its extensive similarity in domain structure and function to DnaJ, CbpA has a unique and specific regulatory mechanism mediated through the small protein CbpM. Both CbpA and CbpM are highly conserved in bacteria. Earlier studies showed that CbpM interacts with the N-terminal J-domain of CbpA inhibiting its co-chaperone activity but the structural basis of this interaction is not known. Here, we have combined NMR spectroscopy, site-directed mutagenesis and surface plasmon resonance to characterize the CbpA/CbpM interaction at the molecular level. We have determined the solution structure of the CbpA Jdomain and mapped the residues that are perturbed upon CbpM binding. The NMR data defined a broad region on helices α2 and α3 as involved in the interactions. Site-directed mutagenesis has been used to further delineate the CbpA J-domain/CbpM interface. We show that the binding sites of CbpM and DnaK on CbpA J-domain overlap, which suggests a competition between DnaK and CbpMfor binding to CbpA as a mechanism for CbpA regulation. This study also provides the explanation for the specificity of CbpM for CbpA versus DnaJ, by identifying the key residues for differential binding.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Biotechnology Research Institute
Peer reviewedYes
NRC number50685
NPARC number16512452
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Record identifierb1c8f8ac-de34-473d-8848-b0ee52d0583b
Record created2010-12-14
Record modified2016-05-09
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