Download MendeleyStructural Basis for Sialoglycan Binding by the Streptococcus sanguinis SrpA Adhesin.
Bensing, B.A., Loukachevitch, L.V., McCulloch, K.M., Yu, H., Vann, K.R., Wawrzak, Z., Anderson, S., Chen, X., Sullam, P.M., Iverson, T.M.(2016) J Biol Chem 291: 7230-7240
- PubMed: 26833566
- DOI: https://doi.org/10.1074/jbc.M115.701425
- Primary Citation of Related Structures:
5EQ2, 5EQ3, 5EQ4 - PubMed 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.
Organizational 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.
