The calcium induced conformation and glycosylation of Gp340’s SRCR domains influences the high affinity interaction with antigen I/II homologs [Molecular Bases of Disease]

June 12th, 2014 by Purushotham, S., Deivanayagam, C.

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 calcium increases the conformational stability of the scavenger rich cysteine repeat domains (SRCRs) of Gp340. Our results also show that AgI/II adheres specifically with nano-molar 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 non-competitively adhere. Compared to the single SRCR domain, the three tandem SRCR domains displayed collective/co-operative increase in their bacterial adherence and aggregation. The SRCRP2 peptide that was earlier shown (not by the authors) to aggregate several oral streptococci displayed limited aggregation and also non-specific adherence compared to the 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 onset of infections.
  • Posted in Journal of Biological Chemistry, Publications
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