Serotonin transporter-ibogaine complexes illuminate mechanisms of inhibition and transport.
Nature May 1, 2019 Jonathan A Coleman, Dongxue Yang, Zhiyu Zhao et al. 301 citations
The serotonin transporter (SERT) recycles serotonin into neurons, and its inhibition by drugs like selective serotonin reuptake inhibitors treats depression and anxiety. Using cryo-electron microscopy, the structures of SERT bound to ibogaine—a natural compound with psychoactive and anti-addictive properties—were captured in three conformations: outward-open, occluded, and inward-open. Ibogaine binds to the central site, and the transition from outward-open to inward-open involves movements of specific transmembrane helices and partial unwinding of another, creating a pathway for substrate and ion release into the cytoplasm. These structures reveal the conformational changes underlying neurotransmitter transport and how ibogaine inhibits SERT.