Structural Characterization of Competence-Stimulating Peptide Analogues Reveals Key Features for ComD1 and ComD2 Receptor Binding in Streptococcus Pneumoniae

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2018 Aug 21

PMID 30125091

Citations 16

Authors

Yifang Yang

Gabriel Cornilescu

Yftah Tal-Gan

Affiliations

Soon will be listed here.

Abstract

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.

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