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

Jérôme Coutant (1, 2) , Patrick Curmi (2) , Flavio Toma (2) , Jean-Pierre Monti (1)

1 GESVAB - EA 3675 - Groupe d'Etude des Substances Végétales à Activité Biologique
2 LSRB - Laboratoire Structure et Reconnaissance des Biomolécules, EA3637, Université Evry-Val d’Essonne

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.

Domains: Life Sciences [q-bio]

Jérôme Coutant, Patrick Curmi, Flavio Toma, Jean-Pierre Monti. NMR Solution Structure of Neurotensin in Membrane-Mimetic Environments: Molecular Basis for Neurotensin Receptor Recognition ‡. Biochemistry, 2007, 46 (19), pp.5656-5663. ⟨10.1021/bi602567p⟩. ⟨hal-02295435⟩