Yang Yifang, Cornilescu Gabriel, Tal-Gan Yftah
Department of Chemistry , University of Nevada, Reno , 1664 North Virginia Street , Reno , Nevada 89557 , United States.
National Magnetic Resonance Facility at Madison , University of Wisconsin-Madison , 433 Babcock Drive , Madison , Wisconsin 53706 , United States.
Biochemistry. 2018 Sep 11;57(36):5359-5369. doi: 10.1021/acs.biochem.8b00653. Epub 2018 Aug 28.
Streptococcus pneumoniae is an important pathogen that utilizes quorum sensing (QS) to regulate genetic transformation, virulence, and biofilm formation. The competence-stimulating peptide (CSP) is a 17-amino acid signal peptide that is used by S. pneumoniae to trigger QS. S. pneumoniae strains can be divided into two main specificity groups based on the CSP signal they produce (CSP1 or CSP2) and their compatible receptors (ComD1 or ComD2, respectively). Modulation of QS in S. pneumoniae can be achieved by targeting the CSP:ComD interaction using synthetic CSP analogues. However, to rationally design CSP-based QS modulators with enhanced activities, an in-depth understanding of the structural features that are required for receptor binding is needed. Herein, we report a comprehensive in-solution three-dimensional structural characterization of eight CSP1 and CSP2 analogues with varied biological activities using nuclear magnetic resonance spectroscopy. Analysis of these structures revealed two distinct hydrophobic patches required for effective ComD1 and ComD2 binding.
肺炎链球菌是一种重要的病原体，它利用群体感应（QS）来调节基因转化、毒力和生物膜形成。 competence-stimulating肽（CSP）是一种17个氨基酸的信号肽，肺炎链球菌利用它来触发群体感应。根据肺炎链球菌产生的CSP信号（CSP1或CSP2）及其兼容受体（分别为ComD1或ComD2），肺炎链球菌菌株可分为两个主要的特异性组。通过使用合成CSP类似物靶向CSP:ComD相互作用，可以实现对肺炎链球菌群体感应的调节。然而，为了合理设计具有增强活性的基于CSP的群体感应调节剂，需要深入了解受体结合所需的结构特征。在此，我们使用核磁共振光谱报告了八种具有不同生物活性的CSP1和CSP2类似物的全面溶液内三维结构表征。对这些结构的分析揭示了有效结合ComD1和ComD2所需的两个不同的疏水斑块。
