Eric Gouaux, Ph.D.
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
Song X, Jensen MØ, Jogini V, Stein RA, Lee C-H, Mchaourab HS, Shaw DE and Gouaux E. (2018) Mechanism of NMDA receptor channel block by MK-801 and memantine. Nature Epub ahead of print: 18 April 2018
Yoder N, Yoshioka C and Gouaux E. (2018) Gating mechanisms of acid-sensing ion channels. Nature 555:397-401.
Coleman JA and Gouaux E. (2018) Structural basis for recognition of diverse antidepressants by the human serotonin transporter. Nature Struct. Mol. Biol. 25:170-175.
Chen S, Zhao Y, Wang Y, Shekhar M, Tajkhorshid E, Gouaux E. (2017) Activation and desensitization mechanism of AMPA receptor-TARP complex by cryo-EM. Cell 170:1234-1246.e14.
Lü W*, Du J*, Goehring A, Gouaux E. (2017) Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation. Science 355 pii:eaal3729. (*co-first author)
Coleman JA, Green EM and Gouaux E. (2016) Thermostabilization, expression, purification, and crystallization of the human serotonin transporter bound to S-citalopram. J. Vis. Exp. Nov 27;(117) doi: 10.3791/54792.
Zhu S and Gouaux E. (2017) Structure and symmetry inform gating principles of ionotropic glutamate receptors. Neuropharmacology 112(Pt A):11-15.
Mansoor SE, Lü W, Oosterheert W, Shekhar M, Tajkhorshid E, Gouaux E. (2016) X-ray structures define human P2X3 receptor gating cycle and antagonist action. Nature 538:66-71.
Zhao Y, Chen S, Yoshioka C, Baconguis I, Gouaux E. (2016) Architecture of fully occupied GluA2 AMPA receptor–TARP complex elucidated by cryo-EM. Nature 536:108-111.
Zhu S, Stein RA, Yoshioka C, Lee CH, Goehring A, Mchaourab HS, Gouaux E. (2016) Mechanism of NMDA receptor inhibition and activation. Cell 165:704-714.
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.
Wang H, Goehring A, Wang KH, Penmatsa A, Ressler R and Gouaux E. (2013) Structural basis for action by diverse antidepressants on biogenic amine transporters. Nature 503:141-145.
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.