Snapshot of an activated peptide receptor

Abstract

Developing therapeutic drugs that target peptide receptors is challenging. The structure of one of these G-protein-coupled receptors, NTS1, activated and bound to a peptide, provides an excellent starting point. See Article p.508 Neurotensin is a short peptide that can act as a neurotransmitter, a digestive hormone, and a regulator of cardiac output and blood pressure. In this manuscript, the authors solve an X-ray crystal structure of the carboxy-terminal portion of neurotensin bound to a rat neurotensin receptor. This is the first structure of a member of the beta group of class A G-protein-coupled receptors (GPCRs), and the first published structure of a GPCR bound to a peptide agonist. This structure should facilitate the development of non-peptide drugs that could be used to treat neurological disorders, cancer and obesity.