title: Active sites of ligands and their receptors are made of common peptides that are also found elsewhere.
abstract: The simultaneous emergence in evolution of a ligand and its receptor might have entailed their active sites being drawn from the pool of common oligopeptides. This was tested on the principal components of cell-matrix interaction: the RGD (Arg-Gly-Asp) site of matrix proteins and the EKKD (Gly-Lys-Lys-Asp) site of integrin cell-surface receptor. In the 32 diverse proteins scrutinized, which totalled 14,806 residues, there were 104 Arg-Gly dipeptides. Most common of the tripeptides beginning with Arg-Gly were Arg-Gly-Leu, Arg-Gly-Gly, and Arg-Gly-Asp; each was found in ten copies. RGD tripeptide was one of the commonest; the fortuitous presence of an RGD site was noted in two enzymes, fibrinogen, a pituitary hormone precursor, and a viral structural protein. The 32 proteins also contained 121 Lys-Lys dipeptides. Of the tetrapeptides centered by Lys-Lys, the commonest was Lys-Lys-Lys-Lys, in four copies. Second most common were Gly-Lys-Lys-Lys, Val-Lys-Lys-Leu, and Glu-Lys-Lys-Asp; each occurred in three copies. The fortuitous presence of an EKKD site was noted in three proteins--an intracellular transport protein, a pituitary hormone precursor and a protein of the cerebrospinal fluid. In most instances, protein-protein interaction between the fortuitously present active sites appears to bring about deleterious consequences. Occasionally, however, the fortuitous active site appears to confer a new function to a protein bearing it.
authors.affiliation: Department of Theoretical Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010-0269.
authors.forename: S
authors.initials: S
authors.lastname: Ohno
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008969:Molecular Sequence Data; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*; D017421:Sequence Analysis
chemical_list: D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear