title: Fine Mapping of the Interaction between C4b-Binding Protein and Outer Membrane Proteins LigA and LigB of Pathogenic Leptospira interrogans.
abstract: The complement system consists of more than 40 proteins that participate in the inflammatory response and in pathogen killing. Complement inhibitors are necessary to avoid the excessive consumption and activation of this system on host cells. Leptospirosis is a worldwide zoonosis caused by spirochetes from the genus Leptospira. Pathogenic leptospires are able to escape from complement activation by binding to host complement inhibitors Factor H [FH] and C4b-binding protein (C4BP) while non-pathogenic leptospires are rapidly killed in the presence of fresh serum. In this study, we demonstrate that complement control protein domains (CCP) 7 and 8 of C4BP α-chain interact with the outer membrane proteins LcpA, LigA and LigB from the pathogenic leptospire L. interrogans. The interaction between C4BP and LcpA, LigA and LigB is sensitive to ionic strength and inhibited by heparin. We fine mapped the LigA and LigB domains involved in its binding to C4BP and heparin and found that both interactions are mediated through the bacterial immunoglobulin-like (Big) domains 7 and 8 (LigA7-8 and LigB7-8) of both LigA and LigB and also through LigB9-10. Therefore, C4BP and heparin may share the same binding sites on Lig proteins.
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Leandro C D
authors.initials: LC
authors.lastname: Breda
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Ching-Lin
authors.initials: CL
authors.lastname: Hsieh
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Mónica M
authors.initials: MM
authors.lastname: Castiblanco Valencia
authors.affiliation: Laboratory of Bacteriology, Institute Butantan, São Paulo, Brazil.
authors.forename: Ludmila B
authors.initials: LB
authors.lastname: da Silva
authors.affiliation: Laboratory of Bacteriology, Institute Butantan, São Paulo, Brazil.
authors.forename: Angela S
authors.initials: AS
authors.lastname: Barbosa
authors.affiliation: Department of Translational Medicine, Division of Medical Protein Chemistry, Lund University, Malmo, Sweden.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
authors.forename: Yung-Fu
authors.initials: YF
authors.lastname: Chang
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Chang
authors.initials: C
authors.lastname: Yung-Fu
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Isaac
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D050716:Complement C4b-Binding Protein / Q000276:immunology / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007921:Leptospira interrogans / Q000276:immunology / Q000378:metabolism*; D025941:Protein Interaction Mapping
chemical_list: D001425:Bacterial Outer Membrane Proteins; D050716:Complement C4b-Binding Protein