TY - JOUR
T1 - Structural basis for sialoglycan binding by the streptococcus sanguinis SrpA adhesin
AU - Bensing, Barbara A.
AU - Loukachevitch, Lioudmila V.
AU - Mcculloch, Kathryn M.
AU - Yu, Hai
AU - Vann, Kendra R.
AU - Wawrzak, Zdzislaw
AU - Anderson, Spencer
AU - Chen, Xi
AU - Sullam, Paul M.
AU - Iverson, T. M.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Streptococcus sanguinis is 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. sanguinis expresses 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.
AB - Streptococcus sanguinis is 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. sanguinis expresses 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.
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U2 - 10.1074/jbc.M115.701425
DO - 10.1074/jbc.M115.701425
M3 - Article
C2 - 26833566
AN - SCOPUS:84964881952
VL - 291
SP - 7230
EP - 7240
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 14
ER -