The conformation of neurotensin bound to its G protein-coupled receptor

Sorin Luca, Jim F. White, Awinder K. Sohal, Dmitri V. Filippov, Jacques H. Van Boom, Reinhard Grisshammer, Marc Baldus

Research output: Contribution to journalArticlepeer-review

210 Scopus citations


G protein-coupled receptors (GPCRs) mediate the perception of smell, light, taste, and pain. They are involved in signal recognition and cell communication and are some of the most important targets for drug development. Because currently no direct structural information on high-affinity ligands bound to GPCRs is available, rational drug design is limited to computational prediction combined with mutagenesis experiments. Here, we present the conformation of a high-affinity peptide agonist (neurotensin, NT) bound to its GPCR NTS-1, determined by direct structural methods. Functional receptors were expressed in Escherichia coli, purified in milligram amounts by using optimized procedures, and subsequently reconstituted into lipid vesicles. Solid-state NMR experiments were tailored to allow for the unequivocal detection of microgram quantities of 13C,15N-labeled NT(8-13) in complex with functional NTS-1. The NMR data are consistent with a disordered state of the ligand in the absence of receptor. Upon receptor binding, the peptide undergoes a linear rearrangement, adopting a β-strand conformation. Our results provide a viable structural template for further pharmacological investigations.

Original languageEnglish (US)
Pages (from-to)10706-10711
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number19
StatePublished - Sep 16 2003
Externally publishedYes

ASJC Scopus subject areas

  • General


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