Recognition of Neurohormones of the NPY Family by Their Receptors

In this review a structural approach developed to answer the question whether hormones from the neuropeptide Y (NPY) family are recognized directly from solution or from the membrane-bound state is described. The chosen strategy is built onto a comparison of a set of peptides with well-known pharmacology and investigates whether similarities of structures of pharmacologically related peptides are higher in solution or in the membrane-bound state. Moreover, we have established the membrane-association mode of these peptides and contributed to our understanding of the structural features of these hormones both when placed in bulk solution and when bound to membranes. As a result we propose a receptor recognition pathway that includes initial association with the membrane and requires the peptides to come off the membrane to diffuse into the binding pocket of the receptor. This review also presents methodology recently developed by us to simulate the structural transition the peptides undergo when diffusing from bulk solution onto the membrane.