| Download | - View accepted manuscript: Structure of CbpA J-domain bound to the regulatory protein CbpM explains its specificity and suggests evolutionary link between CbpM and transcriptional regulators (PDF, 1.7 MiB)
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| DOI | Resolve DOI: https://doi.org/10.1371/journal.pone.0100441 |
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| Author | Search for: Sarraf, Naghmeh S.1; Search for: Shi, Rong; Search for: McDonald, Laura1; Search for: Baardsnes, Jason1; Search for: Zhang, Linhua; Search for: Cygler, Miroslaw; Search for: Ekiel, Irena1 |
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| Affiliation | - National Research Council of Canada. Human Health Therapeutics
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| Format | Text, Article |
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| Subject | CbpA protein; CbpM protein; chaperone; heat shock protein 40; MerR like family; protein DnaJ; protein DnaK; unclassified drug; binding competition; binding site; complex formation; crystal structure; enzyme specificity; protein binding; protein domain; protein protein interaction; protein subunit; regulatory mechanism |
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| Abstract | CbpA is one of the six E. coli DnaJ/Hsp40 homologues of DnaK co-chaperones and the only one that is additionally regulated by a small protein CbpM, conserved in γ-proteobacteria. CbpM inhibits the co-chaperone and DNA binding activities of CbpA. This regulatory function of CbpM is accomplished through reversible interaction with the N-terminal Jdomain of CbpA, which is essential for the interaction with DnaK. CbpM is highly specific for CbpA and does not bind DnaJ despite the high degree of structural and functional similarity between the J-domains of CbpA and DnaJ. Here we report the crystal structure of the complex of CbpM with the J-domain of CbpA. CbpM forms dimers and the J-domain of CbpA interacts with both CbpM subunits. The CbpM-binding surface of CbpA is highly overlapping with the CbpA interface for DnaK, providing a competitive model for regulation through forming mutually exclusive complexes. The structure also provides the explanation for the strict specificity of CbpM for CbpA, which we confirmed by making mutants of DnaJ that became regulated by CbpM. Interestingly, the structure of CbpM reveals a striking similarity to members of the MerR family of transcriptional regulators, suggesting an evolutionary connection between the functionally distinct bacterial cochaperone regulator CbpM and the transcription regulator HspR. |
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| Publication date | 2014-06-19 |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NPARC number | 21272786 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 054260a5-9712-47cb-924b-5924ffd1c11d |
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| Record created | 2014-12-03 |
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| Record modified | 2020-06-04 |
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