title: The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs.
abstract: Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the surface protein antigen I/II (AgI/II) and its homologs as the first step in pathogenesis. Studying this interaction using recombinant proteins, we observed that calcium increases the conformational stability of the scavenger-rich cysteine repeat (SRCRs) domains of GP340. Our results also show that AgI/II adheres specifically with nanomolar affinity to the calcium-induced SRCR conformation in an immobilized state and not in solution. This interaction is significantly dependent on the O-linked carbohydrates present on the SRCRs. This study also establishes that a single SRCR domain of GP340 contains the two surfaces to which the apical and C-terminal regions of AgI/II noncompetitively adhere. Compared with the single SRCR domain, the three tandem SRCR domains displayed a collective/cooperative increase in their bacterial adherence and aggregation. The previously described SRCRP2 peptide that was shown to aggregate several oral streptococci displayed limited aggregation and also nonspecific adherence compared to SRCR domains. Finally, we show distinct species-specific adherence/aggregation between Streptococcus mutans AgI/II and Streptococcus gordonii SspB in their interaction with the SRCRs. This study concludes that identification of the metal ion and carbohydrate adherence motifs on both SRCRs and AgI/II homologs could lead to the development of anti-adhesive inhibitors that could deter the adherence of pathogenic oral streptococci and thereby prevent the onset of infections.
authors.affiliation: From the Department of Vision Sciences/Center for Structural Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-4400.
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Purushotham
authors.affiliation: From the Department of Vision Sciences/Center for Structural Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-4400 champy@uab.edu.
authors.forename: Champion
authors.initials: C
authors.lastname: Deivanayagam
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism; D001422:Bacterial Adhesion / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D006031:Glycosylation; D006801:Humans; D008958:Models, Molecular; D009055:Mouth / Q000382:microbiology; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D054773:Streptococcus gordonii / Q000378:metabolism / Q000472:pathogenicity; D013295:Streptococcus mutans / Q000378:metabolism / Q000472:pathogenicity; D025521:Tumor Suppressor Proteins
chemical_list: D000942:Antigens, Bacterial; D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D002118:Calcium
keywords: Bacterial Adherence, Antigen I/II, Streptococcus mutans, Streptococcus gordonii, Oral Streptococci; Bacterial Adhesion; Bacterial Pathogenesis; Calcium; Cell Surface Protein; Cell Surface Receptor; Glycosylation; Innate Immunity; Surface Plasmon Resonance (SPR)