title: Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L (CbpL) Contributing to Pneumococcal Pathogenesis.
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 Ca2+-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.
authors.affiliation: Department of Crystallography and Structural Biology, "Rocasolano" Institute of Physical-Chemistry, CSIC, Serrano 119, E-28006-Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Gutiérrez-Fernández
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University of Greifswald, D-17487 Greifswald, Germany.
authors.forename: Malek
authors.initials: M
authors.lastname: Saleh
authors.affiliation: Department of Crystallography and Structural Biology, "Rocasolano" Institute of Physical-Chemistry, CSIC, Serrano 119, E-28006-Madrid, Spain.
authors.forename: Martín
authors.initials: M
authors.lastname: Alcorlo
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University of Greifswald, D-17487 Greifswald, Germany.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gómez-Mejía
authors.affiliation: Department of Biological Physical Chemistry. "Rocasolano" Institute of Physical-Chemistry, CSIC, Serrano 119, E-28006-Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Pantoja-Uceda
authors.affiliation: Department of Biological Physical Chemistry. "Rocasolano" Institute of Physical-Chemistry, CSIC, Serrano 119, E-28006-Madrid, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Treviño
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University of Greifswald, D-17487 Greifswald, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Voß
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University of Greifswald, D-17487 Greifswald, Germany.
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Abdullah
authors.affiliation: Department of Crystallography and Structural Biology, "Rocasolano" Institute of Physical-Chemistry, CSIC, Serrano 119, E-28006-Madrid, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Galán-Bartual
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University of Greifswald, D-17487 Greifswald, Germany.
authors.forename: Jolien
authors.initials: J
authors.lastname: Seinen
authors.affiliation: Department of Biomedical Sciences, Unidad Asociada al IQM-CSIC, Universidad de Alcalá, E-28871 Alcalá de Henares, Madrid, Spain.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Sánchez-Murcia
authors.affiliation: Department of Biomedical Sciences, Unidad Asociada al IQM-CSIC, Universidad de Alcalá, E-28871 Alcalá de Henares, Madrid, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Gago
authors.affiliation: Department of Biological Physical Chemistry. "Rocasolano" Institute of Physical-Chemistry, CSIC, Serrano 119, E-28006-Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Bruix
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University of Greifswald, D-17487 Greifswald, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
authors.affiliation: Department of Crystallography and Structural Biology, "Rocasolano" Institute of Physical-Chemistry, CSIC, Serrano 119, E-28006-Madrid, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Hermoso
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism / Q000382:microbiology; D002794:Choline / Q000378:metabolism*; D018360:Crystallography, X-Ray / Q000379:methods; D005260:Female; D057131:Immune Evasion / Q000502:physiology; D051379:Mice; D008958:Models, Molecular; D009305:Nasopharynx / Q000378:metabolism / Q000382:microbiology; D010586:Phagocytes / Q000378:metabolism / Q000382:microbiology; D010767:Phosphorylcholine / Q000378:metabolism; D011008:Pneumococcal Infections / Q000378:metabolism* / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000378:metabolism / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000378:metabolism* / Q000472:pathogenicity*; D013682:Teichoic Acids / Q000378:metabolism*; D014774:Virulence / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D013682:Teichoic Acids; D010767:Phosphorylcholine; D002794:Choline; D002118:Calcium