Background

Eric Gouaux completed his B.A. and Ph.D. degrees in Chemistry at Harvard University in 1984 and 1989, respectively. He remained at Harvard for a year as a postdoctoral fellow and then continued his postdoctoral studies at the Massachusetts Institute of Technology. In 1993, he was appointed assistant professor at the University of Chicago Department of Biochemistry and Molecular Biology.

In 1996, Gouaux joined the Department of Biochemistry and Molecular Biology at Columbia University as an assistant professor. In 2000, he was appointed Investigator with the Howard Hughes Medical Institute and associate professor with Columbia, reaching full professor the following year. Gouaux came to Oregon Health & Science University in 2005 as a Senior Scientist at the Vollum Institute and continuing his position with Howard Hughes. He joined the graduate faculty in the Department of Biochemistry and Molecular Biology in 2006. In 2015, Gouaux was appointed the Jennifer and Bernard Lacroute Term Chair in Neuroscience Research.

 

Summary of Current Research

The work in the Gouaux Lab is concentrated on developing molecular mechanisms for the function of receptors and transporters at chemical synapses. At chemical synapses, neurotransmitters released from one neuron diffuse throughout a small space—the synaptic cleft—to receptors on adjacent neurons. At many synapses, the neurotransmitter binds to a receptor that is a ligand-gated ion channel, and this binding event leads to the opening of a transmembrane pore, which in turn results in depolarization of the nerve cell and generation of an electrical signal. Neurotransmitter transporters surrounding the synapse clear the transmitters from the cleft by coupling the thermodynamically unfavorable uptake to the favorable co-transport of one or more sodium ions.

Glutamate, glycine and the biogenic amines are neurotransmitters of particular significance and currently we are focusing our efforts on eukaryotic glutamate receptors and on bacterial homologs of the transporters for glutamate, glycine and the biogenic amines. While our primary tool is x-ray crystallography, we also utilize electrophysiology as well as other biophysical and biochemical methods.

Recent Publications and Preprints

Coleman JA*, Yang D*, Zhao Z, Wen PC, Yoshioka C, Tajkhorshid E, Gouaux E. (2019) Serotonin transporter-ibogaine complexes illuminate mechanisms of inhibition and transport. Nature Apr 24. doi: 10.1038/s41586-019-1135-1. [Epub ahead of print] (*contributed equally to this work)

Zhao Y, Chen S, Swensen AC, Qian WJ, Gouaux E. (2019) Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM. Science pii:eaaw8250 [Epub ahead of print].

Navratna V, Gouaux E. (2019) Insights into the mechanism and pharmacology of neurotransmitter sodium symporters. Curr. Opin. Struct. Biol. 54:161-170.

Chen S, Gouaux E. (2019) Structure and mechanism of AMPA receptor - auxiliary protein complexes. Curr. Opin. Struct. Biol. 54:104-111.

Jalali-Yazdi F, Chowdhury S, Yoshioka C, Gouaux E. (2018) Mechanisms for zinc and proton inhibition of the GluN1/GluN2A NMDA receptor. Cell 175:1520-1532.e15.

Yoder N, Gouaux E. (2018) Divalent cation and chloride ion sites of chicken acid sensing ion channel 1a elucidated by x-ray crystallography. PLoS One 13:e0202134 eCollection 2018.

Ge J, Elferich J, Goehring A, Zhao J, Schuck P, Gouaux E. (2018) Structure of mouse protocadherin 15 of the stereocilia tip link in complex with LHFPL5. eLife 7:e38770.

Phulera S, Zhu H, Yu J, Claxton DP, Yoder N, Craig Yoshioka C, Gouaux E. (2018) Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABA_A receptor in complex with GABA. eLife 7:e39383.

Claxton DP, Gouaux E. (2018) Expression and purification of a functional heteromeric GABAA receptor for structural studies. PLoS One 13:e0201210 eCollection 2018.

Navratna V, Tosh DK, Jacobson KA, Gouaux E. (2018) Thermostabilization and purification of the human dopamine transporter (hDAT) in an inhibitor and allosteric ligand bound conformation. PLoS One 13:e0200085 eCollection 2018.

Selected Publications

Ge J, Elferich J, Goehring A, Zhao J, Schuck P, Gouaux E. (2018) Structure of mouse protocadherin 15 of the stereocilia tip link in complex with LHFPL5. eLife 7:e38770.

Du J, Lü W, Wu S, Cheng Y, Gouaux E. (2015) Glycine receptor mechanism elucidated by electron cryo-microscopy. Nature 526:224-229.

Wang KH, Penmatsa A, Gouaux E. (2015) Neurotransmitter and psychostimulant recognition by the dopamine transporter. Nature 521:322-327.

Chen L, Dürr KL, Gouaux E. (2014) X-ray structures of AMPA receptor-cone snail toxin complexes illuminate activation mechanism. Science 345:1021-1026.

Lee CH, Lü W, Michel JC, Goehring A, Du J, Song X, Gouaux E. (2014) NMDA receptor structures reveal subunit arrangement and pore architecture. Nature 511:191-197.

Penmatsa A, Wang KH, and Gouaux E. (2013) X-ray structure of dopamine transporter elucidates antidepressant mechanism. Nature 503:85-90.

Hattori M and Gouaux E. (2012) Molecular mechanism of ATP binding and ion channel activation in P2X receptors. Nature 485:207-212.

Krishnamurthy H and Gouaux E. (2012) X-ray structures of LeuT in substrate-free outward-open and apo inward-open states. Nature 481:469-474.

Hibbs RE and Gouaux E. (2011) Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474:54-60.

Sobolevsky AI, Rosconi MP and Gouaux E. (2009) X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor. Nature 462:745-56.