衔接蛋白控制的寡聚化激活AAA+蛋白ClpC。
Adaptor protein controlled oligomerization activates the AAA+ protein ClpC.
作者信息
Kirstein Janine, Schlothauer Tilman, Dougan David A, Lilie Hauke, Tischendorf Gilbert, Mogk Axel, Bukau Bernd, Turgay Kürşad
机构信息
FB Biologie, Chemie, Pharmazie, Institut für Biologie, Freie Universität Berlin, Berlin, Germany.
出版信息
EMBO J. 2006 Apr 5;25(7):1481-91. doi: 10.1038/sj.emboj.7601042. Epub 2006 Mar 9.
Abstract
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.
摘要
AAA+蛋白ClpC不仅参与错误折叠和聚集蛋白的清除，还通过调节蛋白水解作用控制革兰氏阳性菌枯草芽孢杆菌中几个发育过程的关键步骤。与其他AAA+蛋白不同，ClpC在没有像MecA这样的衔接蛋白的情况下无法介导这些过程。在这里，我们证明ClpC的全面激活基于MecA参与由ClpC和衔接蛋白组成的活性且能识别底物的高级寡聚体组装的能力，这是该AAA+蛋白所有活性的先决条件。利用ClpA和ClpC的杂交蛋白，我们确定了ClpC第一个AAA+结构域的N端和连接结构域是与MecA相互作用的关键位点。这种新的衔接蛋白介导机制为AAA+蛋白生物活性的调节增加了另一层控制。
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