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Title: Structures of the Streptococcus sanguinis SrpA Binding Region with Human Sialoglycans Suggest Features of the Physiological Ligand

Journal Article · · Biochemistry
 [1];  [2];  [3];  [4];  [3];  [2];  [1]
  1. Vanderbilt Univ., Nashville, TN (United States)
  2. Univ. of California, San Francisco, CA (United States); Northern California Institute for Research and Education, San Francisco, CA (United States)
  3. Univ. of California, Davis, CA (United States)
  4. Univ. of California, Davis, CA (United States); Henan Inst. of Science and Technology, Xinxiang (China)
+ Show Author Affiliations

Streptococcus sanguinis is a leading cause of bacterial infective endocarditis, a life-threatening infection of heart valves. S. sanguinis binds to human platelets with high avidity, and this adherence is likely to enhance virulence. Previous studies suggest that a serine-rich repeat adhesin termed SrpA mediates the binding of S. sanguinis to human platelets via its interaction with sialoglycans on the receptor GPIbα. However, in vitro binding assays with SrpA and defined sialoglycans failed to identify specific high-affinity ligands. To improve our understanding of the interaction between SrpA and human platelets, we determined cocrystal structures of the SrpA sialoglycan binding region (SrpABR) with five low-affinity ligands: three sialylated trisaccharides (sialyl-T antigen, 3'-sialyllactose, and 3'-sialyl-N-acetyllactosamine), a sialylated tetrasaccharide (sialyl-LewisX), and a sialyl galactose disaccharide component common to these sialoglyans. We then combined structural analysis with mutagenesis to further determine whether our observed interactions between SrpABR and glycans are important for binding to platelets and to better map the binding site for the physiological receptor. Here, we found that the sialoglycan binding site of SrpABR is significantly larger than the sialoglycans cocrystallized in this study, which suggests that binding of SrpA to platelets either is multivalent or occurs via a larger, disialylated glycan.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Inst. of Health; Michigan Economic Development Corp.; Michigan Technology Tri-Corridor; American Heart Association
Grant/Contract Number:
AC02-06CH11357; S10 RR026915; 085P1000817; AI41513; AI106987; 14GRNT20390021
OSTI ID:
1331707
Journal Information:
Biochemistry, Vol. 55, Issue 42; ISSN 0006-2960
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 15 works
Citation information provided by
Web of Science

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Cited By (8)

Structural basis for the role of serine-rich repeat proteins from Lactobacillus reuteri in gut microbe–host interactions journal March 2018
Streptococcus oralis subsp. dentisani Produces Monolateral Serine-Rich Repeat Protein Fibrils, One of Which Contributes to Saliva Binding via Sialic Acid journal July 2019
Mycoplasma genitalium adhesin P110 binds sialic-acid human receptors journal October 2018
Streptococcal Siglec-like adhesins recognize different subsets of human plasma glycoproteins: implications for infective endocarditis journal June 2018
Recognition of specific sialoglycan structures by oral streptococci impacts the severity of endocardial infection journal June 2019
Serine-rich repeat proteins from gut microbes journal April 2019
Serine-Rich Repeat Adhesins Mediate Shear-Enhanced Streptococcal Binding to Platelets journal March 2018
Streptococcus sanguinis biofilm formation & interaction with oral pathogens journal June 2018

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59 BASIC BIOLOGICAL SCIENCES
carbohydrates
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cells
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receptors