ABSTRACT

To the PE_PGRS protein subfamily belongs a group of surface-exposed mycobacterial antigens that in Mycobacterium tuberculosis (Mtb) H37Rv accounts to more than 65 genes, 51 of which are thought to express a functional protein. PE_PGRS proteins share a conserved structural architecture with three main domains: the N-terminal PE domain; the PGRS domain, that can vary in sequence and size and is characterized by the presence of multiple GGA-GGX amino acid repeats; the highly conserved sequence containing the GRPLI motif that links the PE and PGRS domains; the unique C-terminus end that can vary in size from few to up to ≈ 300 amino acids. pe_pgrs genes emerged in slow-growing mycobacteria and expanded and diversified in MTBC and few other pathogenic mycobacteria. Interestingly, despite sequence homology and apparent redundancy, PE_PGRS proteins seem to have evolved a peculiar function. In this review, we summarize the actual knowledge on this elusive protein family in terms of evolution, structure, and function, focusing on the role of PE_PGRS in TB pathogenesis. We provide an original hypothesis on the role of the PE domain and propose a structural model for the polymorphic PGRS domain that might explain how so similar proteins can have different physiological functions.

摘要

PE_PGRS蛋白亚家族属于一组表面暴露的分枝杆菌抗原，在结核分枝杆菌（Mtb）中，H37Rv涉及65个以上的基因，其中51个被认为表达功能蛋白。PE_PGRS蛋白具有三个主要结构域的保守结构结构：N-末端PE结构域；PGRS结构域，其序列和大小可以变化，并且特征在于存在多个GGA-GGX氨基酸重复序列；含有连接PE和PGRS结构域的GRPLI基序的高度保守的序列；独特的C末端末端，其大小可能从几个到大约300个氨基酸不等。pe_pgrs基因出现在生长缓慢的分枝杆菌中，并在MTBC和其他少数病原性分枝杆菌中扩展和多样化。有趣的是，尽管有序列同源性和明显的冗余性，PE_PGRS蛋白似乎已经进化出独特的功能。在这篇综述中，我们从进化，结构和功能的角度总结了有关这种难以捉摸的蛋白质家族的实际知识，重点是PE_PGRS在结核病发病机理中的作用。我们提供了关于PE结构域的作用的原始假设，并提出了多态性PGRS结构域的结构模型，该模型可以解释相似蛋白质如何具有不同的生理功能。