Dienstag, 16. Oktober 2018, 16:30 - 17:45 iCal

Guest Lecture by Jonathan Coleman (Gouaux-Lab)

Structures of the human serotonin transporter in complex with antidepressants and ibogaine

UZA 2, Lecture Hall 6
Althanstraße 14, 1090 Vienna



is pleased to invite you to the following lecture

'Structures of the human serotonin transporter in complex with antidepressants and ibogaine' by Jonathan COLEMAN, PhD

Vollum Institute (Gouaux Lab), Postdoctoral Fellow, Oregon Health & Science University

on: Tuesday, October 16th, 2018, 04:30 pm (16:30 Uhr)

at: UZA 2, Althanstr. 14, 1090 Vienna, Lecture Hall 6

ABSTRACT: The serotonin transporter (SERT) terminates signaling through the sodium-and chloride-dependent reuptake of neurotransmitter into presynaptic neurons. Neurotransmitter transporters utilize an alternating access mechanism in which conformational changes expose a central substrate binding site to each side of the membrane. Ibogaine is a hallucinogenic drug that is thought to non-competitively inhibit transport. By contrast, most antidepressants competitively inhibit SERT by binding to the central site, locking the transporter in an outward-open conformation. While recent x-ray structures of SERT have revealed the mechanism of antidepressant inhibition, the mechanism of neurotransmitter transport still remains elusive. Remarkably, single particle cryo-EM structures of SERT in the presence of ibogaine have captured the transporter in three distinct conformational states– outward-open, occluded, and inward open. Analysis of the resulting structures shows how movements of groups of helices are associated with transport, thus defining the structural rearrangements which occur from the outward to the inward states and illuminating the mechanism of neurotransmitter transport.



Postdoctoral Fellow, Oregon Health & Science University (PI: Eric Gouaux, Ph.D.); e-mail: colemajo@ohsu.edu

• Determined the three-dimensional structure of the human serotonin transporter in complex with antidepressants using x-ray crystallography.

• Mapped the secondary binding site in neurotransmitter transporters and showed binding of allosteric ligands can slow dissociation of primary site ligands.

• Developed cryo-EM techniques to solve structures of small membrane transporters to beyond 4 Å resolution.

• Deciphered how ibogaine non-competitively inhibits serotonin transport by cryo-EM of SERT-ibogaine complexes and showed ibogaine populates the outward-open, occluded, and inward states.

Resulted in 4 publications, 3 first-author (Nature, Nat. Struct. Mol. Biol., J. Vis. Exp.) and 1 manuscript in review. Awarded funding from a Banting Postdoctoral Fellowship.

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MolTag Doctoral Program


Susanne Menschik-Zunzer
Department of Pharmacology and Toxicology, UZA 2
DK Molecular Drug Targets
01 4277 55320
susanne.menschik-zunzer@univie.ac.at, office.moltag@univie.ac.at