Conformational ensembles: the role of neuropeptide structures in receptor binding.
Conformational properties of several similar FMRFamide-like neuropeptides from mollusks were investigated by nuclear magnetic resonance (NMR) spectroscopy. It was found that amino acid substitutions in the N-terminal variable regions of the peptides had dramatic effects on the populations of reverse turns in solution. The populations of turns, as measured by two independent NMR parameters, were found to be highly correlated (r(2) = 0.93 and 0. 82) with IC(50) values using receptor membrane preparations from Helix aspersa (Payza, 1987; Payza et al., 1989). These results suggest that the amount of turn in the free peptide can influence the receptor binding affinities of that peptide. On the basis of these observations, a model was developed in which only a single species from a conformational ensemble of an unbound peptide will bind to a particular receptor. Thus, the conformational ensemble reduces the effective concentration of a particular peptide with respect to a particular receptor.
Edison
A S
AS
Department of Biochemistry, Center for Structural Biology, University of Florida Brain Institute, National High Magnetic Field Laboratory, University of Florida, Gainesville, Florida 32610-0245, USA.
Espinoza
E
E
Zachariah
C
C
D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution; D000818:Animals; D019835:FMRFamide / Q000737:chemistry; D006372:Helix, Snails / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008968:Molecular Conformation; D009479:Neuropeptides / Q000737:chemistry* / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism*
D009479:Neuropeptides; D011956:Receptors, Cell Surface; D019835:FMRFamide