Streptococcus pyogenes binds to the extracellular matrix (ECM) and a variety of host cells and tissues, causing diverse human diseases. Protein 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 precisely and compare their functions and binding sites in Fn. The minimal functional unit of RD2 is of 44 amino acids, with contributions from two adjacent RD2 repeats flanked by a novel ‘MGGQSES’ motif. 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 higher affinity than RD2, and recognizes a larger fragment that contains fibrin and collagen binding domains. Expression of UR and RD2 independently on the surface‐exposed region of unrelated streptococcal protein demonstrates that both mediate adherence of the bacteria to the ECM. We describe here a mechanism of adherence of a pathogen that involves two pairs of sites located on a single adhesin molecule and directed at the same host receptor.

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Abstract. To determine the role of each intracellular domain of the fibronectin receptor in receptor distribution, chimeric receptors were constructed containing the human interleukin-2 receptor (gp55 subunit) as the extracellular and transmembrane domains, in combination with either the a5 or ß, intracellular domain of the fibronectin receptor as the cytoplasmic domain . These chimeric receptors were transiently expressed in normal fibroblasts, and their localization on the cell surface was determined by immunofluorescence using antibodies to the human interleukin-2 receptor. The a5 chimera was expressed diffusely on the plasma membrane . The 01 chimera, however, colocalized with the endogenous fibronectin receptor at focal contacts of cells spread on fibronectin . On cells spread in the presence of serum, the 01 chimera colocalized both with the fibronectin receptor at sites of extracellular fibronectin fibrils and with the vitronectin receptor at focal contacts. The 01 intracellular domain alone, therefore, contains sufficient information to target the chimeric receptor to regions of the cell where ligandoccupied integrin receptors are concentrated. The find-T HE integrins, a family of transmembrane heterodimeric receptors consisting of a and ß subunits, play a central role in cell adhesion and migration . These processes are important in development, wound healing, metastasis, and other biological events. Integrins function in both cell-cell and cell-substratum adhesion . Integrin heterodimers can be classified into subfamilies based on the different ß subunits. Different combinations of a and ß subunits give rise to receptors with different ligand specificities, including receptors for fibronectin, vitronectin, collagen, and laminin. Although some integrins are cell-type specific, most function in many cell types, and most cell types express a variety ofintegrin receptors, allowing them to interact with many extracellular matrix components (recent reviews include Akiyama et al

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