Cell adhesion to streptavidin via RGD-dependent integrins.
Biotin-blocked streptavidin binds specifically (Kd approximately 3 x 10(-8) M) to cell surfaces, presumably via an RYD-containing sequence. This site is distinct from the biotin-binding cleft of the protein and bears high homology to the RGD-containing cell-binding domain of fibronectin. We show here that various cell types adhere to immobilized streptavidin and that the soluble protein interferes specifically with cell adhesion to fibronectin substrata (with an IC50 of about 1 x 10(-7) M) but less so to other adhesive glycoproteins (e.g., collagen type I, vitronectin). Immunochemical evidence combined with peptide competition studies demonstrated that cells bind to streptavidin primarily via the major fibronectin receptor (the alpha 5 beta 1 integrin). The results suggest that streptavidin acts as a relatively strict fibronectin mimetic, thus reflecting the great similarity in their respective RYD/RGD sequence and the immediate flanking regions. The bacterial protein emulates and competes with fibronectin and other extracellular matrix adhesive proteins in the initial recognition and binding to cell surfaces, but appears not to induce subsequent processes (e.g., anchorage and spreading). Streptavidin may thus represent a novel example of bacterial protein mimicry of a key adhesion motif.
Alon
R
R
Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Bayer
E A
EA
Wilchek
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D001710:Biotin; D002448:Cell Adhesion; D002460:Cell Line; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides; D017469:Receptors, Fibronectin / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D018000:Receptors, Peptide; D019809:Streptavidin
D001426:Bacterial Proteins; D016023:Integrins; D009842:Oligopeptides; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; C051382:arginyl-glycyl-aspartic acid directed cell adhesion receptor; D001710:Biotin; C047981:arginyl-glycyl-aspartic acid; D019809:Streptavidin