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复杂的结构-功能关系:革兰氏阴性菌中HtrA家族蛋白的案例

Intricate Structure-Function Relationships: The Case of the HtrA Family Proteins from Gram-Negative Bacteria.

作者信息

Zarzecka Urszula, Skorko-Glonek Joanna

机构信息

Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland.

出版信息

Int J Mol Sci. 2024 Dec 7;25(23):13182. doi: 10.3390/ijms252313182.

DOI:10.3390/ijms252313182
PMID:39684892
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11642142/
Abstract

Proteolytic enzymes play key roles in living organisms. Because of their potentially destructive action of degrading other proteins, their activity must be very tightly controlled. The evolutionarily conserved proteins of the HtrA family are an excellent example illustrating strategies for regulating enzymatic activity, enabling protease activation in response to an appropriate signal, and protecting against uncontrolled proteolysis. Because HtrA homologs play key roles in the virulence of many Gram-negative bacterial pathogens, they are subject to intense investigation as potential therapeutic targets. Model HtrA proteins from bacterium are allosteric proteins with reasonably well-studied properties. Binding of appropriate ligands induces very large structural changes in these enzymes, including changes in the organization of the oligomer, which leads to the acquisition of the active conformation. Properly coordinated events occurring during the process of HtrA activation ensure proper functioning of HtrA and, consequently, ensure fitness of bacteria. The aim of this review is to present the current state of knowledge on the structure and function of the exemplary HtrA family proteins from Gram-negative bacteria, including human pathogens. Special emphasis is paid to strategies for regulating the activity of these enzymes.

摘要

蛋白水解酶在生物体中发挥着关键作用。由于它们具有降解其他蛋白质的潜在破坏作用,其活性必须受到非常严格的控制。HtrA家族进化保守的蛋白质就是一个很好的例子,它说明了调节酶活性、响应适当信号激活蛋白酶以及防止不受控制的蛋白水解的策略。由于HtrA同源物在许多革兰氏阴性细菌病原体的毒力中起关键作用,它们作为潜在的治疗靶点受到了深入研究。来自细菌的典型HtrA蛋白是具有研究得相当充分的性质的别构蛋白。适当配体的结合会在这些酶中诱导非常大的结构变化,包括寡聚体组织的变化,这会导致获得活性构象。HtrA激活过程中发生的适当协调的事件确保了HtrA的正常功能,从而确保了细菌的适应性。本综述的目的是介绍革兰氏阴性细菌(包括人类病原体)中典型HtrA家族蛋白的结构和功能的当前知识状态。特别强调了调节这些酶活性的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f003/11642142/29267b074518/ijms-25-13182-g010.jpg
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