Evidence for a C-terminal structural motif in gastrin and its bioactive fragments in membrane mimetic media

Backbone HN chemical shift temperature variance, Hα chemical shift deviations and complex non-sequential NOE patterns pointed to the C-terminal of [Nle15] gastrin-17 adopting an ordered conformation. Distance geometry calculations and NOE-restrained molecular dynamics simulations in membrane mimetic solvent boxes of decane and water indicated the C-terminal tetrapeptide sequence of all three peptides adopted a similar, well defined structure, with a general type IV β-turn observed for all three peptides. The conformation of [Nle15] gastrin-17 consisted of two short helices between Leu5-Glu9 and Ala11-Trp14, with the one helix terminating in a type I β-turn spanning Gly13-Asp16. The experimental evidence and conformational characteristics of the three peptides in micellar media support a membrane-associated mechanism of receptor recognition and activation for the gastrin hormone family and furthermore point to a possible biologically relevant structural motif for gastrin activity.