The cell surfaces of many bacteria carry filamentous polypeptides termed adhesins that enable binding to both biotic and abiotic surfaces. Surface adherence is facilitated by the exquisite selectivity of the adhesins for their cognate ligands or receptors and is a key step in niche or host colonization and pathogenicity. Streptococcus gordonii is a primary colonizer of the human oral cavity and an opportunistic pathogen, as well as a leading cause of infective endocarditis in humans. The fibrillar adhesin CshA is an important determinant of S. gordonii adherence, forming peritrichous fibrils on its surface that bind host cells and other microorganisms. CshA possesses a distinctive multidomain architecture comprising an N-terminal target-binding region fused to 17 repeat domains (RDs) that are each ∼100 amino acids long. Here, using structural and biophysical methods, we demonstrate that the intact CshA repeat region (CshA_RD1-17, domains 1-17) forms an extended polymeric monomer in solution. We recombinantly produced a subset of CshA RDs and found that they differ in stability and unfolding behavior. The NMR structure of CshA_RD13 revealed a hitherto unreported all β-fold, flanked by disordered interdomain linkers. These findings, in tandem with complementary hydrodynamic studies of CshA_RD1-17, indicate that this polypeptide possesses a highly unusual dynamic transitory structure characterized by alternating regions of order and disorder. This architecture provides flexibility for the adhesive tip of the CshA fibril to maintain bacterial attachment that withstands shear forces within the human host. It may also help mitigate deleterious folding events between neighboring RDs that share significant structural identity without compromising mechanical stability.

中文翻译：

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链球菌多域原纤维粘附素 CshA 具有细长的聚合结构。


许多细菌的细胞表面携带称为粘附素的丝状多肽，能够结合生物和非生物表面。粘附素对其同源配体或受体的精细选择性促进了表面粘附，并且是利基或宿主定植和致病性的关键步骤。戈登链球菌是人类口腔的主要定植菌和机会致病菌，也是人类感染性心内膜炎的主要原因。纤维状粘附素 CshA 是戈登沙门氏菌粘附的重要决定因素，在其表面形成周毛原纤维，结合宿主细胞和其他微生物。 CshA 具有独特的多结构域结构，包括与 17 个重复结构域 (RD) 融合的 N 端靶标结合区，每个重复结构域长约 100 个氨基酸。在这里，使用结构和生物物理方法，我们证明完整的 CshA 重复区域（CshA_RD1-17，结构域 1-17）在溶液中形成延伸的聚合单体。我们重组产生了 CshA RD 的一个子集，发现它们在稳定性和展开行为方面有所不同。 CshA_RD13 的 NMR 结构揭示了迄今为止未报道的全 β 折叠，两侧是无序的域间连接子。这些发现与 CshA_RD1-17 的补充流体动力学研究相结合，表明该多肽具有一种非常不寻常的动态瞬时结构，其特征是有序和无序区域交替。这种结构为 CshA 原纤维的粘合尖端提供了灵活性，以维持细菌附着，从而承受人体宿主内的剪切力。它还可能有助于减轻具有重要结构特性的相邻 RD 之间的有害折叠事件，而不会影响机械稳定性。