The Nonideal Coiled Coil of M Protein and Its Multifarious Functions in Pathogenesis
The Nonideal Coiled Coil of M Protein and Its Multifarious Functions in Pathogenesis
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DOI：
10.1007/978-94-007-0940-9_12
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发表时间：
2011-01-01
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影响因子：
--
通讯作者：
Ghosh, Partho
中科院分区：
文献类型：
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作者：
Ghosh, Partho
M蛋白是A组化脓性链球菌的主要毒力因子。这种革兰氏阳性细菌病原体导致轻度感染，如咽炎，以及严重侵袭性疾病，如链球菌中毒性休克综合征。M蛋白通过多种方式促进GAS毒力，包括阻断抗体和补体的沉积，帮助形成微集落，中和抗菌肽，以及触发促炎和促凝状态。这些功能是由M蛋白与许多宿主成分，特别是C4BP和纤维蛋白原相互作用而确定的。前一种相互作用在许多抗原性变异的M蛋白类型中是保守的，但以一种惊人的序列无关的方式发生，而后者在M1蛋白类型中与严重侵袭性疾病有关。值得注意的是，对于一种具有如此多样化相互作用的蛋白质来说，M蛋白有一个相对简单但不理想的阿尔法螺旋卷曲序列。这种序列的非理想性是M蛋白的一个重要特征。不理想的残基会导致其卷曲螺旋结构中的特殊不规则，这对于与纤维蛋白原相互作用和建立促炎状态是必不可少的。此外，这些结构异常让人想起肌球蛋白和原肌球蛋白，这两种蛋白是GAS感染自身免疫后遗症患者交叉反应抗体的靶点。
The M protein is a major virulence factor of Streptococcus pyogenes (group A Streptococcus, GAS). This gram-positive bacterial pathogen is responsible for mild infections, such as pharyngitis, and severe invasive disease, like streptococcal toxic shock syndrome. M protein contributes to GAS virulence in multifarious ways, including blocking deposition of antibodies and complement, helping formation of microcolonies, neutralizing antimicrobial peptides, and triggering a proinflammatory and procoagulatory state. These functions are specified by interactions between M protein and many host components, especially C4BP and fibrinogen. The former interaction is conserved among many antigenically variant M protein types but occurs in a strikingly sequence-independent manner, and the latter is associated in the M1 protein type with severe invasive disease. Remarkably for a protein of such diverse interactions, the M protein has a relatively simple but nonideal alpha-helical coiled coil sequence. This sequence nonideality is a crucial feature of M protein. Nonideal residues give rise to specific irregularities in its coiled-coil structure, which are essential for interactions with fibrinogen and establishment of a proinflammatory state. In addition, these structural irregularities are reminiscent of those in myosin and tropomyosin, which are targets for crossreactive antibodies in patients suffering from autoimmune sequelae of GAS infection.