Structure of the agonist-bound neurotensin receptor
Copyright policy )Structure of the agonist-bound neurotensin receptor
Neurotensin (NTS) is a 13-amino-acid peptide that functions as both a neurotransmitter and a hormone through the activation of the neurotensin receptor NTSR1, a G-protein-coupled receptor (GPCR). In the brain, NTS modulates the activity of dopaminergic systems, opioid-independent analgesia, and the inhibition of food intake; in the gut, NTS regulates a range of digestive processes. Here we present the structure at 2.8 Å resolution of Rattus norvegicus NTSR1 in an active-like state, bound to NTS(8-13), the carboxy-terminal portion of NTS responsible for agonist-induced activation of the receptor. The peptide agonist binds to NTSR1 in an extended conformation nearly perpendicular to the membrane plane, with the C terminus oriented towards the receptor core. Our findings provide, to our knowledge, the first insight into the binding mode of a peptide agonist to a GPCR and may support the development of non-peptide ligands that could be useful in the treatment of neurological disorders, cancer and obesity.
Models, Molecular, Binding Sites, Protein Conformation, Amino Acid Motifs, Crystallography, X-Ray, Article, Rats, Mutation, Animals, Bacteriophage T4, Receptors, Neurotensin, Muramidase, Amino Acid Sequence, Neurotensin
Models, Molecular, Binding Sites, Protein Conformation, Amino Acid Motifs, Crystallography, X-Ray, Article, Rats, Mutation, Animals, Bacteriophage T4, Receptors, Neurotensin, Muramidase, Amino Acid Sequence, Neurotensin
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