title: Structural Basis for Sialoglycan Binding by the Streptococcus sanguinis SrpA Adhesin.
abstract: Streptococcus sanguinisis a leading cause of infective endocarditis, a life-threatening infection of the cardiovascular system. An important interaction in the pathogenesis of infective endocarditis is attachment of the organisms to host platelets.S. sanguinisexpresses a serine-rich repeat adhesin, SrpA, similar in sequence to platelet-binding adhesins associated with increased virulence in this disease. In this study, we determined the first crystal structure of the putative binding region of SrpA (SrpABR) both unliganded and in complex with a synthetic disaccharide ligand at 1.8 and 2.0 Å resolution, respectively. We identified a conserved Thr-Arg motif that orients the sialic acid moiety and is required for binding to platelet monolayers. Furthermore, we propose that sequence insertions in closely related family members contribute to the modulation of structural and functional properties, including the quaternary structure, the tertiary structure, and the ligand-binding site.
authors.affiliation: From the Division of Infectious Diseases, Veterans Affairs Medical Center, Department of Medicine, University of California, San Francisco and the Northern California Institute for Research and Education, San Francisco, California 94121.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Bensing
authors.affiliation: the Departments of Pharmacology and.
authors.forename: Lioudmila V
authors.initials: LV
authors.lastname: Loukachevitch
authors.affiliation: the Departments of Pharmacology and.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: McCulloch
authors.affiliation: the Department of Chemistry, University of California, Davis, California 95616, and.
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.affiliation: Biochemistry.
authors.forename: Kendra R
authors.initials: KR
authors.lastname: Vann
authors.affiliation: Life Sciences Collaborative Access Team, Synchrotron Research Center, Northwestern University, Argonne, Illinois 60439.
authors.forename: Zdzislaw
authors.initials: Z
authors.lastname: Wawrzak
authors.affiliation: Life Sciences Collaborative Access Team, Synchrotron Research Center, Northwestern University, Argonne, Illinois 60439.
authors.forename: Spencer
authors.initials: S
authors.lastname: Anderson
authors.affiliation: the Department of Chemistry, University of California, Davis, California 95616, and.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: From the Division of Infectious Diseases, Veterans Affairs Medical Center, Department of Medicine, University of California, San Francisco and the Northern California Institute for Research and Education, San Francisco, California 94121.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Sullam
authors.affiliation: the Departments of Pharmacology and Biochemistry, Center for Structural Biology, and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232, tina.iverson@vanderbilt.edu.
authors.forename: T M
authors.initials: TM
authors.lastname: Iverson
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D004696:Endocarditis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013290:Streptococcal Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D013291:Streptococcus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D037521:Virulence Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D037521:Virulence Factors; D019158:N-Acetylneuraminic Acid
keywords: Streptococcus; adhesin; bacterial adhesion; bacterial pathogenesis; carbohydrate-binding protein; crystal structure; immunoglobulin-like domain; lectin; sialic acid
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