Cryo-EM reveals two distinct serotonin-bound conformations of full-length 5-HT_3A receptor.

ABSTRACT: The 5-HT_3A serotonin receptor¹, a cationic pentameric ligand-gated ion channel (pLGIC), is the clinical target for management of nausea and vomiting associated with radiation and chemotherapies². Upon binding, serotonin induces a global conformational change that encompasses the ligand-binding extracellular domain (ECD), the transmembrane domain (TMD) and the intracellular domain (ICD), the molecular details of which are unclear. Here we present two serotonin-bound structures of the full-length 5-HT_3A receptor in distinct conformations at 3.32 Å and 3.89 Å resolution that reveal the mechanism underlying channel activation. In comparison to the apo 5-HT_3A receptor, serotonin-bound states underwent a large twisting motion in the ECD and

SUBMITTER: Basak S 

PROVIDER: S-EPMC6237196 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature