Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis Journal Article


Author(s): Gutierrez-Fernandez, Javier; Saleh, Malek; Alcorlo, Martín; Gómez Mejóa, Alejandro; Pantoja-Uceda, David; Treviño, Miguel A; Vob, Franziska; Abdullah, Mohammed R; Galán-Bartual, Sergio; Seinen, Jolien; Sánchez-Murcia, Pedro A; Gago, Federico; Bruix, Marta; Hammerschmidt, Sven; Hermoso, Juan Antonio
Article Title: Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis
Affiliation IST Austria
Abstract: The human pathogen Streptococcus pneumoniae is decorated with a special class of surface-proteins known as choline-binding proteins (CBPs) attached to phosphorylcholine (PCho) moieties from cell-wall teichoic acids. By a combination of X-ray crystallography, NMR, molecular dynamics techniques and in vivo virulence and phagocytosis studies, we provide structural information of choline-binding protein L (CbpL) and demonstrate its impact on pneumococcal pathogenesis and immune evasion. CbpL is a very elongated three-module protein composed of (i) an Excalibur Ca 2+ -binding domain -reported in this work for the very first time-, (ii) an unprecedented anchorage module showing alternate disposition of canonical and non-canonical choline-binding sites that allows vine-like binding of fully-PCho-substituted teichoic acids (with two choline moieties per unit), and (iii) a Ltp-Lipoprotein domain. Our structural and infection assays indicate an important role of the whole multimodular protein allowing both to locate CbpL at specific places on the cell wall and to interact with host components in order to facilitate pneumococcal lung infection and transmigration from nasopharynx to the lungs and blood. CbpL implication in both resistance against killing by phagocytes and pneumococcal pathogenesis further postulate this surface-protein as relevant among the pathogenic arsenal of the pneumococcus.
Journal Title: Scientific Reports
Volume: 6
ISSN: 20452322
Publisher: Nature Publishing Group  
Date Published: 2016-12-05
Copyright Statement: CC BY 4.0
URL:
DOI: 10.1038/srep38094
Notes: We gratefully acknowledge Karsta Barnekow and Kristine Sievert-Giermann, for technical assistance and Lothar Petruschka for in silico analysis (all Dept. of Genetics, University of Greifswald). We are further grateful to the staff from SLS synchrotron beamline for help in data collection. This work was supported by grants from the Deutsche Forschungsgemeinschaft DFG GRK 1870 (to SH) and the Spanish Ministry of Economy and Competitiveness (BFU2014-59389-P to JAH, CTQ2014-52633-P to MB and SAF2012-39760-C02-02 to FG) and S2010/BMD-2457 (Community of Madrid to JAH and FG).
Open access: yes (OA journal)