Journal Article

Cryo-EM structure of 5-HT3A receptor in its resting conformation

Taylor, Derek J., Gicheru, Yvonne, Basak, Sandip, Samanta, Amrita, Fuente, Maria la de, Molugu, Sudheer Kumar, Huang, Wei, Nieman, Marvin T., Chakrapani, Sudha, Hughes, Taylor, Moiseenkova-Bell, Vera

2018

Overview

Serotonin receptors (5-HT 3A R) directly regulate gut movement, and drugs that inhibit 5-HT 3A R function are used to control emetic reflexes associated with gastrointestinal pathologies and cancer therapies. The 5-HT 3A R function involves a finely tuned orchestration of three domain movements that include the ligand-binding domain, the pore domain, and the intracellular domain. Here, we present the structure from the full-length 5-HT 3A R channel in the apo-state determined by single-particle cryo-electron microscopy at a nominal resolution of 4.3 Å. In this conformation, the ligand-binding domain adopts a conformation reminiscent of the unliganded state with the pore domain captured in a closed conformation. In comparison to the 5-HT 3A R crystal structure, the full-length channel in the apo-conformation adopts a more expanded conformation of all the three domains with a characteristic twist that is implicated in gating. Serotonin receptor (5-HT 3A R), a pentameric ligand-gated ion channel, regulates numerous gastrointestinal functions. Here the authors provide a cryo-electron microscopic structure from the full-length 5-HT 3A R in the apo-state which corresponds to a resting conformation of the channel.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 101/28 / 631/45/535/1258/1259 / 631/57/2270/1140 / Binding / Cancer / Channel gating / Crystal structure / Electron microscopy / Humanities and Social Sciences / Ligands / multidisciplinary / Receptor mechanisms / Receptors / Reflexes / Science / Science (multidisciplinary) / Serotonin / Serotonin receptors / Serotonin S3 receptors