Jiang Jialiu, Schmitz Karl R
Department of Chemistry and Biochemistry, University of Delaware, Newark, DE, United States.
Department of Biological Sciences, University of Delaware, Newark, DE, United States.
Front Microbiol. 2023 Apr 17;14:1161764. doi: 10.3389/fmicb.2023.1161764. eCollection 2023.
All clades of bacteria possess Hsp100/Clp family unfoldase enzymes that contribute to aspects of protein quality control. In Actinomycetota, these include ClpB, which functions as an independent chaperone and disaggregase, and ClpC, which cooperates with the ClpP1P2 peptidase to carry out regulated proteolysis of client proteins. We initially sought to algorithmically catalog Clp unfoldase orthologs from Actinomycetota into ClpB and ClpC categories. In the process, we uncovered a phylogenetically distinct third group of double-ringed Clp enzymes, which we term ClpI. ClpI enzymes are architecturally similar to ClpB and ClpC, with intact ATPase modules and motifs associated with substrate unfolding and translation. While ClpI possess an M-domain similar in length to that of ClpC, its N-terminal domain is more variable than the strongly conserved N-terminal domain of ClpC. Surprisingly, ClpI sequences are divisible into sub-classes that either possess or lack the LGF-motifs required for stable assembly with ClpP1P2, suggesting distinct cellular roles. The presence of ClpI enzymes likely provides bacteria with expanded complexity and regulatory control over protein quality control programs, supplementing the conserved roles of ClpB and ClpC.
所有细菌进化枝都拥有Hsp100/Clp家族的解折叠酶，这些酶在蛋白质质量控制方面发挥作用。在放线菌门中，这些酶包括作为独立伴侣蛋白和解聚酶发挥作用的ClpB，以及与ClpP1P2肽酶协同作用以对底物蛋白进行调控性蛋白水解的ClpC。我们最初试图通过算法将放线菌门中的Clp解折叠酶直系同源物分类为ClpB和ClpC类别。在此过程中，我们发现了一组在系统发育上截然不同的第三类双环Clp酶，我们将其命名为ClpI。ClpI酶在结构上与ClpB和ClpC相似，具有完整的ATP酶模块以及与底物解折叠和翻译相关的基序。虽然ClpI拥有一个长度与ClpC相似的M结构域，但其N端结构域比ClpC保守的N端结构域更具变异性。令人惊讶的是，ClpI序列可分为具有或缺乏与ClpP1P2稳定组装所需的LGF基序的亚类，这表明其具有不同的细胞功能。ClpI酶的存在可能为细菌在蛋白质质量控制程序方面提供了更大的复杂性和调控能力，补充了ClpB和ClpC的保守功能。
