Over One Hundred Peptide-Activated G Protein-Coupled Receptors Recognize Ligands with Turn Structure

G protein-coupled receptors (GPCRs) constitute the largest family of cellular receptors involved in signal transduction. A review is given of the voluminous structural and/or activity evidence in support of a ligand turn shape being the likely recognition domain in GPCR-binding domains of all of these ligands. In the absence of structurally defined GPCR-ligand complexes, solution or solid-state structures are analyzed for a variety of GPCR-binding ligands alone, including (i) peptide and protein hormone ligands, (ii) bioactive peptide fragments, (iii) cyclic peptides, often analogous of protein segments, (iv) peptidomimetic antagonists with a conformational bias enforced by the presence of turn-inducing constraints. Examples of small cyclic peptidomimetics for naturally occurring GPCR-binding small peptides are also covered, including, somatosatin (14 residues), melanocyte-stimulating hormone (13), oxytocin (9), vasopressin (9), substance P (11), bradykinin (9), opiod peptides, and small fragments of proteins.