Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, 3086, Australia.
Sci Rep. 2019 Dec 2;9(1):18019. doi: 10.1038/s41598-019-53736-8.
The ClpP protease is found in all kingdoms of life, from bacteria to humans. In general, this protease forms a homo-oligomeric complex composed of 14 identical subunits, which associates with its cognate ATPase in a symmetrical manner. Here we show that, in contrast to this general architecture, the Clp protease from Mycobacterium smegmatis (Msm) forms an asymmetric hetero-oligomeric complex ClpP1P2, which only associates with its cognate ATPase through the ClpP2 ring. Our structural and functional characterisation of this complex demonstrates that asymmetric docking of the ATPase component is controlled by both the composition of the ClpP1 hydrophobic pocket (Hp) and the presence of a unique C-terminal extension in ClpP1 that guards this Hp. Our structural analysis of ClpP1 also revealed openings in the side-walls of the inactive tetradecamer, which may represent sites for product egress.
ClpP 蛋白酶存在于从细菌到人类的所有生命领域。一般来说，这种蛋白酶形成由 14 个相同亚基组成的同型寡聚体复合物，以对称的方式与它的同源 ATP 酶结合。在这里，我们表明，与这种一般结构相反，来自耻垢分枝杆菌（Msm）的 Clp 蛋白酶形成不对称的异源寡聚体复合物 ClpP1P2，它仅通过 ClpP2 环与同源 ATP 酶结合。我们对该复合物的结构和功能表征表明，ATP 酶成分的不对称对接受 ClpP1 疏水口袋（Hp）的组成和 ClpP1 中独特的 C 末端延伸的存在控制，后者保护该 Hp。我们对 ClpP1 的结构分析还揭示了无活性十四聚体侧壁上的开口，这可能代表产物出口的位点。
