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

Gutierrez-Fernandez, Javier and Saleh, Malek and Alcorlo, Martín and Gómez Mejóa, Alejandro and Pantoja-Uceda, David and Treviño, Miguel Á and Vob, Franziska and Abdullah, Mohammed R and Galán-Bartual, Sergio and Seinen, Jolien and Sánchez-Murcia, Pedro A and Gago, Federico and Bruix, Marta and Hammerschmidt, Sven and Hermoso, Juan Antonio (2016) Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis. Scientific Reports, 6. ISSN 2045-2322

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Official URL: http://dx.doi.org/10.1038/srep38094

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.

Item Type: Article
DOI: 10.1038/srep38094
Subjects: 500 Science > 570 Life sciences; biology > 576 Genetics and evolution
600 Technology > 610 Medicine and health
Research Group: Sazanov Group
SWORD Depositor: Sword Import User
Depositing User: Sword Import User
Date Deposited: 16 Jan 2017 07:58
Last Modified: 30 Aug 2017 08:01
URI: https://repository.ist.ac.at/id/eprint/735

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