TY - JOUR
T1 - Glucan binding protein C of Streptococcus mutans mediates both sucrose-independent and sucrose-dependent adherence
AU - Mieher, Joshua L.
AU - Larson, Matthew R.
AU - Schormann, Norbert
AU - Purushotham, Sangeetha
AU - Wu, Ren
AU - Rajashankar, Kanagalaghatta R.
AU - Wu, Hui
AU - Deivanayagam, Champion
N1 - Funding Information:
We are grateful to Jeffrey Banas, University of Iowa, for providing us with a plasmid that encoded the full-length GbpC. J.L.M., M.R.L., N.S., S.P., and C.D. are grateful to all the core facilities at the University of Alabama at Birmingham, including the Comprehensive Cancer Center's Structural Biology shared facility, Heflin Center for Genomic Sciences and Proteomics and Mass Spectrometry. This work is based upon research conducted at the Southeast Regional Collaborative Access Team (SER-CAT) 22-ID beamline and at the Northeastern Collaborative Access Team (NE-CAT) 24-ID-C and 24-ID-E beamlines, which are funded by the National Institute of General Medical Sciences from the National Institutes of Health (P41 GM103403). This research used resources of the Advanced Photon Source. Use of the Advanced Photon Source is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract number W-31-109-Eng-38. J.L.M. is a T-90 fellow and is supported by the NIH/NIDCR T-90DE022736-06; J.L.M. (previously) and C.D. were partially supported through NIH/NIAID R21AI105038. R.W. and H.W. were partially supported by NIH/NIDCR grants R01DE022350 and R01DE017954. We declare that we have no conflicts of interest. J.L.M. conducted all ITC and SPR experiments and resolved the cocrystal structure with N.S. and cowrote the manuscript; M.L.R. cloned, expressed, purified, and crystallized the GbpC fragments and cowrote the manuscript. S.P. initially contributed to ITC and BIAcore experiments, R.W. carried out mutational analysis and biofilm studies, K.R.R. collected X-ray data and obtained initial maps of the structure, H.W. conceived all biologically relevant data and cowrote manuscript, and C.D. conceived ideas, grew crystals, collected data, refined the structures, and prepared the manuscript for publication.
Publisher Copyright:
© 2018 American Society for Microbiology.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - The high-resolution structure of glucan binding protein C (GbpC) at 1.14 Å, a sucrose-dependent virulence factor of the dental caries pathogen Streptococcus mutans, has been determined. GbpC shares not only structural similarities with the V regions of AgI/II and SspB but also functional adherence to salivary agglutinin (SAG) and its scavenger receptor cysteine-rich domains (SRCRs). This is not only a newly identified function for GbpC but also an additional fail-safe binding mechanism for S. mutans. Despite the structural similarities with S. mutans antigen I/II (AgI/II) and SspB of Streptococcus gordonii, GbpC remains unique among these surface proteins in its propensity to adhere to dextran/glucans. The complex crystal structure of GbpC with dextrose (β-D-glucose; Protein Data Bank ligand BGC) highlights exclusive structural features that facilitate this interaction with dextran. Targeted deletion mutant studies on GbpC's divergent loop region in the vicinity of a highly conserved calcium binding site confirm its role in biofilm formation. Finally, we present a model for adherence to dextran. The structure of GbpC highlights how artfully microbes have engineered the lectin-like folds to broaden their functional adherence repertoire.
AB - The high-resolution structure of glucan binding protein C (GbpC) at 1.14 Å, a sucrose-dependent virulence factor of the dental caries pathogen Streptococcus mutans, has been determined. GbpC shares not only structural similarities with the V regions of AgI/II and SspB but also functional adherence to salivary agglutinin (SAG) and its scavenger receptor cysteine-rich domains (SRCRs). This is not only a newly identified function for GbpC but also an additional fail-safe binding mechanism for S. mutans. Despite the structural similarities with S. mutans antigen I/II (AgI/II) and SspB of Streptococcus gordonii, GbpC remains unique among these surface proteins in its propensity to adhere to dextran/glucans. The complex crystal structure of GbpC with dextrose (β-D-glucose; Protein Data Bank ligand BGC) highlights exclusive structural features that facilitate this interaction with dextran. Targeted deletion mutant studies on GbpC's divergent loop region in the vicinity of a highly conserved calcium binding site confirm its role in biofilm formation. Finally, we present a model for adherence to dextran. The structure of GbpC highlights how artfully microbes have engineered the lectin-like folds to broaden their functional adherence repertoire.
KW - Antigen I/II
KW - Fibrillar
KW - Glucan binding protein
KW - Lectin-like fold
KW - Microbial adherence
KW - Polyproline type II helix
KW - Salivary agglutinin
KW - Streptococcus gordonii
KW - Streptococcus mutans
KW - Sucrose-dependent adhesion
KW - Sucrose-independent adhesion
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U2 - 10.1128/IAI.00146-18
DO - 10.1128/IAI.00146-18
M3 - Article
C2 - 29685986
AN - SCOPUS:85050150647
SN - 0019-9567
VL - 86
JO - Infection and Immunity
JF - Infection and Immunity
IS - 7
M1 - e00146-18
ER -