Crystal structure of the human 5-HT_1B serotonin receptor bound to an inverse agonist.

ABSTRACT: 5-hydroxytryptamine (5-HT, also known as serotonin) regulates many physiological processes through the 5-HT receptor family. Here we report the crystal structure of 5-HT_1B subtype receptor (5-HT_1BR) bound to the psychotropic serotonin receptor inverse agonist methiothepin (MT). Crystallization was facilitated by replacing ICL3 with a novel optimized variant of BRIL (OB1) that enhances the formation of intermolecular polar interactions, making OB1 a potential useful tool for structural studies of membrane proteins. Unlike the agonist ergotamine (ERG), MT occupies only the conserved orthosteric binding pocket, explaining the wide spectrum effect of MT on serotonin receptors. Compared with ERG, MT shifts toward TM6 and sterically pushes residues W327^6.48, F330

SUBMITTER: Yin W 

PROVIDER: S-EPMC5847559 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature