Probing Conformational Disorder in Neurotensin by 2D Solid-state NMR and Comparison to MD Simulations

¹ MPI for Biophysical Chemistry

^* To whom correspondence should be addressed. E-mail: maba{at}nmr.mpibpc.mpg.de.

Submitted on January 20, 2005
Revised on March 7, 2005
Accepted on 28 June 2005

	Abstract

An approach is introduced to characterize conformational ensembles of intrinsically unstructured peptides on the atomic level using two-dimensional solid-state NMR data and their combination with molecular dynamics simulations. For neurotensin, a peptide that binds with high affinity to a G-protein coupled receptor, this method permits investigating the changes in conformational preferences of a neurotransmitter transferred from a frozen aqueous solution via a lipid model phase to the receptor-bound form. The results speak against a conformational preorganization of the ligand in detergents in which the receptor has been shown to be functional. Further extensions to the study of protein folding are possible.

Key Words: Conformational Disorder, Magic Angle Spinning, Neurotensin, Solid-state NMR

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