A 2-DOMAIN MECHANISM FOR GROUP-A STREPTOCOCCAL ADHERENCE THROUGH PROTEIN-F TO THE EXTRACELLULAR-MATRIX

Streptococcus pyogenes binds to the extracellular matrix (ECM) and a v ariety of host cells and tissues, causing diverse human diseases. Prot ein F, a S.pyogenes adhesin that binds fibronectin (Fn), contains two binding domains, A repeated domain (RD2) and an additional domain (UR) , located immediately N-terminal to RD2, Both domains are required for maximal Fn binding, In this study, we characterize RD2 and UR precise ly and compare their functions and binding sites in Fn, The minimal fu nctional unit of RD2 is of 44 amino acids, with contributions from two adjacent RD2 repeats flanked by a novel 'MGGQSES' moth, RD2 binds to the N-terminal fibrin binding domain of Fn, UR contains 49 amino acids , of which six are from the first repeat of RD2, It binds to Fn with h igher affinity than RD2, and recognizes a larger fragment that contain s fibrin and collagen binding domains, Expression of UR and RD2 indepe ndently on the surface-exposed region of unrelated streptococcal prote in demonstrates that both mediate adherence of the bacteria to the ECM , We describe here a mechanism of adherence of a pathogen that involve s two pairs of sites located on a single adhesin molecule and directed at the same host receptor.