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.
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Ohno, S. Active sites of ligands and their receptors are made of common peptides that are also found elsewhere. J Mol Evol 40, 102–106 (1995). https://doi.org/10.1007/BF00166601
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DOI: https://doi.org/10.1007/BF00166601