Probing conformational disorder in neurotensin by two-dimensional solid-state NMR and comparison to molecular dynamics simulations.
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 the investigation of 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 pre-organization 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.
Department of NMR-Based Structural Biology, Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Henrike
H
Heise
Sorin
S
Luca
Bert L
BL
de Groot
Helmut
H
Grubmüller
Marc
M
Baldus
D003902:Detergents / Q000494:pharmacology; D005615:Freezing; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D008968:Molecular Conformation; D009496:Neurotensin / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry; D012984:Software; D014867:Water / Q000737:chemistry
D003902:Detergents; D008024:Ligands; D008055:Lipids; D010455:Peptides; D011506:Proteins; D014867:Water; D009496:Neurotensin