Institut de Biologie Structurale Jean-Pierre Ebel, UMR 5075 (CEA, CNRS, UJF), Grenoble, France.
Structure. 2010 Jan 13;18(1):106-15. doi: 10.1016/j.str.2009.10.019.
Pili are fibrous virulence factors associated directly to the bacterial surface that play critical roles in adhesion and recognition of host cell receptors. The human pathogen Streptococcus pneumoniae carries a single pilus-related adhesin (RrgA) that is key for infection establishment and provides protection from bacterial challenge in animal infection models, but details of these roles remain unclear. Here we report the high-resolution crystal structure of RrgA, a 893-residue elongated macromolecule whose fold contains four domains presenting both eukaryotic and prokaryotic origins. RrgA harbors an integrin I collagen-recognition domain decorated with two inserted "arms" that fold into a positively charged cradle, as well as three "stalk-forming" domains. We show by site-specific mutagenesis, mass spectrometry, and thermal shift assays that intradomain isopeptide bonds play key roles in stabilizing RrgA's stalk. The high sequence similarity between RrgA and its homologs in other Gram-positive microorganisms suggests common strategies for ECM recognition and immune evasion.
菌毛是与细菌表面直接相关的纤维状毒力因子，在黏附和识别宿主细胞受体方面发挥着关键作用。人类病原体肺炎链球菌携带一种单一的菌毛相关黏附素（RrgA），它是感染建立的关键，并为动物感染模型中的细菌挑战提供保护，但这些作用的细节仍不清楚。在这里，我们报告了 RrgA 的高分辨率晶体结构，这是一种 893 个残基的长形大分子，其折叠包含四个结构域，呈现出真核和原核的起源。RrgA 含有一个整合素 I 胶原蛋白识别结构域，该结构域上有两个插入的“臂”，折叠成一个带正电荷的摇篮，还有三个“柄形成”结构域。我们通过定点突变、质谱和热移位分析表明，结构域内的异肽键在稳定 RrgA 的柄部方面发挥着关键作用。RrgA 与其在其他革兰氏阳性微生物中的同源物之间的高序列相似性表明了 ECM 识别和免疫逃避的共同策略。
