Song Yingjie, Ke Yitao, Kang Mei, Bao Rui
Center of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China.
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
Comput Struct Biotechnol J. 2021 Dec 8;20:40-49. doi: 10.1016/j.csbj.2021.12.004. eCollection 2022.
Members of the high temperature requirement A (HtrA) protein family are widely distributed amongst prokaryotic and eukaryotic species. HtrA proteins have ATP-independent dual chaperone-protease activity and mediate protein quality control. Emerging evidence indicates that HtrA family members are vital for establishing infections and bacterial survival under stress conditions. Bacterial HtrA proteins are increasingly thought of as important new targets for antibacterial drug development. Recent literature suggests that HtrA protein AlgW from has distinct structural, functional, and regulatory characteristics. The novel dual-signal activation mechanism seen in AlgW is required to modulate stress and drug responses in bacteria, prompting us to review our understanding of the many HtrA proteins found in microorganisms. Here, we describe the distribution of HtrA gene orthologues in pathogenic bacteria, discuss their structure-function relationships, outline the molecular mechanisms exhibited by different bacterial HtrA proteins in bacteria under selective pressure, and review the significance of recently developed small molecule inhibitors targeting HtrA in pathogenic bacteria.
高温需求A（HtrA）蛋白家族成员广泛分布于原核生物和真核生物物种中。HtrA蛋白具有不依赖ATP的双重伴侣蛋白酶活性，并介导蛋白质质量控制。新出现的证据表明，HtrA家族成员对于在应激条件下建立感染和细菌存活至关重要。细菌HtrA蛋白越来越被认为是抗菌药物开发的重要新靶点。最近的文献表明，来自[具体来源未提及]的HtrA蛋白AlgW具有独特的结构、功能和调控特性。AlgW中发现的新型双信号激活机制对于调节细菌中的应激和药物反应是必需的，这促使我们重新审视我们对微生物中发现的众多HtrA蛋白的理解。在这里，我们描述了HtrA基因直系同源物在病原菌中的分布，讨论了它们的结构-功能关系，概述了不同细菌HtrA蛋白在选择性压力下在细菌中表现出的分子机制，并综述了最近开发的针对病原菌中HtrA的小分子抑制剂的意义。
