NMR Solution Structure of Neurotensin in Membrane-Mimetic Environments: Molecular Basis for Neurotensin Receptor Recognition ‡

Abstract : Neurotensin (NT) is a 13-residue neuropeptide that exerts multiple biological functions in thecentral and peripheral nervous system. Little is known about the structure of this neuropeptide, and whatis known only concerns its C-terminal part. We determined here for the first time the structure of thefull-length NT in membrane-mimicking environments by means of classical proton-proton distanceconstraints derived from solution-state NMR spectroscopy. NT was found to have a structure at both itsN and C termini, whereas the central region of NT remains highly flexible. In TFE and HFIP solutions,the NT C-terminus presents an extended slightly incurved structure, whereas in DPC it has a‚turn. TheN-terminal region of NT possesses great adaptability and accessibility to the microenvironment in thethree media studied. Altogether, our work demonstrates a structure of NT fully compatible with its NTR-bound state.