The ‘Chicken and Egg’ Problem of Co-evolution of Peptides and Their Cognate Receptors: Which Came First?

Abstract

As will be evident from the other chapters in this Volume, small peptide molecules regulate a wide variety of biological processes in both vertebrate and invertebrate species. For each bioactive peptide there exists one or more specific membrane-bound receptors, which transduce(s) the signal of peptide binding into a cellular response. The majority of these receptors share a common topology with seven membrane-spanning domains, an extracellular amino terminus and a cytoplasmically located carboxy terminus. Since this class of receptors translates the process of peptide binding into an intracellular response through an interaction with one or more of a family of GTP-binding proteins (G-proteins), they have been named G-protein-coupled receptors (see Probst et al. 1992; Meyerhof et al. 1993). Other types of peptide receptor are known, including those for growth factors, such as epidermal growth factor, which have a single membrane-spanning domain and an intracellular ligand-activated tyrosine kinase domain (see McInnes and Sykes 1997), that for the peptide Phe-Met-Arg-Phe-amide which contains an integral ligand-gated sodium channel (Lingueglia et al. 1995), and the 200-kDa head-activator receptor of hydra which exhibits sequence similarity to members of the low-density lipoprotein receptor family (Hampe et al., this Vol.). The role of the latter may be that of a carrier protein, binding and presenting head-activator, which is a small hydrophobic peptide, to the ‘true’ head-activator receptor.