The tachykinin tale: molecular recognition in a historical perspective

Crystallography, mutational mapping and crosslinking are but a few of the experimental techniques that have helped to elucidate the underlying principles of molecular recognition between macromolecules and to improve our understanding of the evolution of the structure-activity relationship (SAR). While this development has been particularly successful for small and rigid ligands and substrates that bind to larger hydrophilic biomolecules, our understanding of membrane-embedded proteins is still rather limited. This review uses the example of the neuropeptide family of tachykinins and their G-protein coupled receptors (GPCR) to present how complementary experimental strategies over the past decades have nourished and modified conceptual models of the structural requisites of molecular recognition and function. Given the little we know, the pertinent question is how we proceed from here.