title: Variants of the cell recognition site of fibronectin that retain attachment-promoting activity.
abstract: A tetrapeptide sequence, Arg-Gly-Asp-Ser, is the minimal structure recognized by cells in the large, adhesive glycoprotein fibronectin. We now have defined the structural requirements for this cell recognition site by testing several synthetic variants of the active tetrapeptide sequence. The conservative substitutions of lysine for arginine, alanine for glycine, or glutamic acid for aspartic acid each resulted in abrogation of the cell attachment-promoting activity characteristic of the natural sequence. However, in the position of the serine residue, some alterations were compatible with activity. Assay of peptides containing the structure Arg-Gly-Asp-X (where X = another amino acid residue) showed that an Arg-Gly-Asp-Val sequence predicted to be present in some, but not all, fibronectin molecules as a result of alternative RNA splicings could potentially create a second cell attachment site in those fibronectin polypeptide chains carrying that sequence. Other proteins with potentially active Arg-Gly-Asp-X sequences include several proteins that are known to interact with the cell surface. Among these are various types of collagens, thrombin, and discoidin, a slime-mold protein that may be involved in cell aggregation. The result presented here show that the arginine, glycine, and aspartic acid residues are absolutely required for the cell recognition, and that the surrounding amino acids may play a role in the expression of cell attachment activity in fibronectin and other proteins having this sequence. We suggest, based on these data, that this recognition mechanism may be common to a number of biological systems.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D007668:Kidney; D007700:Kinetics; D011485:Protein Binding; D051381:Rats; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D005353:Fibronectins; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D003094:Collagen