Evolution of the PE_PGRS Proteins of Mycobacteria: Are All Equal or Are Some More Equal than Others?

IF 3.6 3区 生物学 Q1 BIOLOGY
Bei Chen, Belmin Bajramović, Bastienne Vriesendorp, Herman Pieter Spaink
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引用次数: 0

Abstract

PE_PGRS domain proteins represent a family of proteins found in pathogenic and non-pathogenic mycobacteria such as M. smegmatis. This conserved family is characterized by two distinct regions denoted as the variable PGRS domain defined by glycine-rich repeats, and a PE domain consisting of two antiparallel alpha-helices. There are many indications that PE_PGRS proteins are involved in immunopathogenesis and virulence by evading or triggering the host immune response. However, there is not yet any information on their degree of specialization or redundancy. Computational analysis and structural annotation using AlphaFold3 combined with other tools reveals an exceptionally powerful and unprecedented ability to undergo phase separation by the PGRS domain. This suggests that PGRS's glycine-rich, multivalent, low-complexity composition supports phase separation while adopting a structured conformation, contrary to the disordered nature typical of such domains. While previously never reported, the hypothesized role of PGRS in virulence indicates a novel window into the seemingly ubiquitous role of phase separation in cellular compartmentalization and molecular dynamics. This review aims to summarize the current understanding of the PE_PGRS family and its various biological roles in the context of bioinformatic analyses of some interesting representatives of M. marinum that are under control by host sterols. Based on the structural bioinformatics analysis, we discuss future approaches to uncover the mechanistic role of this intriguing family of mycobacterial proteins in both pathogenic and non-pathogenic mycobacteria.

分枝杆菌PE_PGRS蛋白的进化:是全部相等还是有些比其他更相等?
PE_PGRS结构域蛋白是在致病性和非致病性分枝杆菌(如耻垢分枝杆菌)中发现的一个蛋白家族。这个保守家族的特征是两个不同的区域,一个是由富含甘氨酸的重复序列定义的可变PGRS结构域,另一个是由两个反平行的α螺旋组成的PE结构域。许多迹象表明,PE_PGRS蛋白通过逃避或触发宿主免疫反应参与免疫发病和毒力。然而,目前还没有关于它们的专业化程度或冗余程度的任何信息。使用AlphaFold3结合其他工具进行计算分析和结构注释,揭示了通过PGRS域进行相分离的异常强大和前所未有的能力。这表明PGRS富含甘氨酸、多价、低复杂性的组成支持相分离,同时采用结构化构象,与此类结构域典型的无序性质相反。虽然以前从未报道过,但PGRS在毒力中的假设作用为细胞区隔化和分子动力学中似乎普遍存在的相分离作用提供了一个新的窗口。本文综述了PE_PGRS家族及其在受宿主甾醇控制的海洋分枝杆菌的生物信息学分析中的各种生物学作用。基于结构生物信息学分析,我们讨论了未来的方法来揭示这个有趣的分枝杆菌蛋白家族在致病性和非致病性分枝杆菌中的机制作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biology-Basel
Biology-Basel Biological Science-Biological Science
CiteScore
5.70
自引率
4.80%
发文量
1618
审稿时长
11 weeks
期刊介绍: Biology (ISSN 2079-7737) is an international, peer-reviewed, quick-refereeing open access journal of Biological Science published by MDPI online. It publishes reviews, research papers and communications in all areas of biology and at the interface of related disciplines. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files regarding the full details of the experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.
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