Middle Tennessee State University, Department of Chemistry, 1301 East Main Street, Murfreesboro, TN 37132, United States.
Middle Tennessee State University, Department of Chemistry, 1301 East Main Street, Murfreesboro, TN 37132, United States.
J Struct Biol. 2018 Jan;201(1):52-62. doi: 10.1016/j.jsb.2017.11.003. Epub 2017 Nov 10.
Regulated proteolysis is required in all organisms for the removal of misfolded or degradation-tagged protein substrates in cellular quality control pathways. The molecular machines that catalyze this process are known as ATP-dependent proteases with examples that include ClpAP and ClpCP. Clp/Hsp100 subunits form ring-structures that couple the energy of ATP binding and hydrolysis to protein unfolding and subsequent translocation of denatured protein into the compartmentalized ClpP protease for degradation. Copies of the clpA, clpC, clpE, clpK, and clpL genes are present in all characterized bacteria and their gene products are highly conserved in structure and function. However, the evolutionary relationship between these proteins remains unclear. Here we report a comprehensive phylogenetic analysis that suggests divergent evolution yielded ClpA from an ancestral ClpC protein and that ClpE/ClpL represent intermediates between ClpA/ClpC. This analysis also identifies a group of proteobacterial ClpC proteins that are likely not functional in regulated proteolysis. Our results strongly suggest that bacterial ClpC proteins should not be assumed to all function identically due to the structural differences identified here.
在所有生物体中，调控蛋白水解对于细胞质量控制途径中去除错误折叠或降解标记的蛋白质底物都是必需的。催化这个过程的分子机器被称为 ATP 依赖性蛋白酶，其例子包括 ClpAP 和 ClpCP。Clp/Hsp100 亚基形成环结构，将 ATP 结合和水解的能量与蛋白质展开以及随后将变性蛋白质易位到分隔的 ClpP 蛋白酶中进行降解偶联。所有已鉴定的细菌都存在 clpA、clpC、clpE、clpK 和 clpL 基因的副本，其基因产物在结构和功能上高度保守。然而，这些蛋白质之间的进化关系尚不清楚。在这里，我们报告了一项全面的系统发育分析，该分析表明，分歧进化导致 ClpA 从祖先 ClpC 蛋白中产生，而 ClpE/ClpL 代表 ClpA/ClpC 之间的中间体。该分析还鉴定了一组可能在调控蛋白水解中不起作用的变形菌 ClpC 蛋白。我们的研究结果强烈表明，由于这里鉴定的结构差异，不能假设细菌 ClpC 蛋白的功能都完全相同。
