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| Subject Categories: Signal Transduction | Proteins |
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| The EMBO Journal
(2006) 25, 1481–1491, doi:10.1038/sj.emboj.7601042 Published online 9 March 2006 |
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| Adaptor protein controlled oligomerization activates the AAA+ protein ClpC |
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Janine Kirstein1, 2, 5, Tilman Schlothauer2, 5, David A Dougan2, 3, Hauke Lilie4, Gilbert Tischendorf1, Axel Mogk2, Bernd Bukau2 and Kür ad Turgay1, 2
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1 FB Biologie, Chemie, Pharmazie, Institut für Biologie, Freie Universität Berlin, Berlin, Germany 2 Zentrum für Molekulare Biologie Heidelberg, Universität Heidelberg, Heidelberg, Germany 3 Department of Biochemistry, La Trobe University, Melbourne, Australia 4 Institut für Biotechnologie, Universität Halle-Wittenberg, Halle (Saale), Germany To whom correspondence should be addressed Kür ad Turgay, FB Biologie, Chemie, Pharmazie, Institut für Biologie, Freie Universität Berlin, Königin-Luise-Str. 12-16, Berlin 14195, Germany. Tel. +49 30 8385 3111; Fax +49 30 8385 3118; E-mail: kturgay@zedat.fu-berlin.de
5 These authors contributed equally to this work Received 17 November 2005; Accepted 21 February 2006; Published online 9 March 2006. |
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| Abstract |
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| The AAA+ protein ClpC is not only involved in the removal of misfolded and aggregated proteins but also controls, through regulated proteolysis, key steps of several developmental processes in the Gram-positive bacterium Bacillus subtilis. In contrast to other AAA+ proteins, ClpC is unable to mediate these processes without an adaptor protein like MecA. Here, we demonstrate that the general activation of ClpC is based upon the ability of MecA to participate in the assembly of an active and substrate-recognizing higher oligomer consisting of ClpC and the adaptor protein, which is a prerequisite for all activities of this AAA+ protein. Using hybrid proteins of ClpA and ClpC, we identified the N-terminal and the Linker domain of the first AAA+ domain of ClpC as the essential MecA interaction sites. This new adaptor-mediated mechanism adds another layer of control to the regulation of the biological activity of AAA+ proteins. |
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| Keywords: AAA+, adaptorprotein, chaperones, HSP100/Clp, proteolysis |
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