西亚试剂：：Structure of the agonist-bound neurotensin receptor

Jim F. White, Nicholas Noinaj, Yoko Shibata, James Love, Brian Kloss, Feng Xu, Jelena Gvozdenovic-Jeremic, Priyanka Shah, Joseph Shiloach, Christopher G. Tate & Reinhard Grisshammer

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 NTS8–13, 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.

丙烯醛肉桂醛桂皮醛4-硝基肉桂醛