Structural Basis of Host Cell Recognition by the Pilus Adhesin from Streptococcus pneumoniae
Structural Basis of Host Cell Recognition by the Pilus Adhesin from Streptococcus pneumoniae
复制标题
DOI：
10.1016/j.str.2009.10.019
复制
发表时间：
2010-01-13
期刊：
影响因子：
5.7
通讯作者：
Dessen, Andrea
中科院分区：
文献类型：
--
作者：
Izore, Thierry;Contreras-Martel, Carlos;Dessen, Andrea
菌毛是直接与细菌表面相关的纤维性毒力因子，在宿主细胞受体的黏附和识别中发挥关键作用。人类病原体肺炎链球菌携带一种单一的毛发相关粘附素(RrgA)，该粘附素在动物感染模型中是感染建立的关键，并提供针对细菌挑战的保护，但这些作用的细节尚不清楚。在这里，我们报告了RrgA的高分辨晶体结构，它是一个893个残基的拉长大分子，其折叠包含四个结构域，分别代表真核和原核来源。RrgA含有一个整合素I型胶原识别结构域，带有两个插入的“臂”，可以折叠成一个带正电荷的摇篮，以及三个“茎形成”结构域。我们通过定点突变、质谱分析和热位移分析表明，结构域内的异肽键在稳定RrgA的茎方面起着关键作用。RrgA与其他革兰氏阳性微生物中RrgA同源物的高度序列相似性表明了ECM识别和免疫逃避的共同策略。
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.