Eric Gouaux, Ph.D.
Senior Scientist, Vollum Institute
Investigator, Howard Hughes Medical Institute
Lab Phone: 503-494-6721
Office: Vollum Institute, Rm 1423A
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, he 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. He 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.
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.
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.
Baconguis I and Gouaux E. (2012) Structural plasticity and dynamic selectivity of acid-sensing ion channel–spider toxin complexes. Nature 489:400-405.
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.
Piscitelli CL, Krishnamurthy H, and Gouaux E. (2010) Neurotransmitter/sodium symporter orthologue LeuT has a single high-affinity substrate site. Nature 468:1129-1132.
Sobolevsky AI, Rosconi MP, and Gouaux E. (2009) X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor. Nature 462:745-756.
Shaffer PL, Goehring A, Shankaranarayanan A, and Gouaux E. (2009) Structure and mechanism of a Na+-independent amino acid transporter. Science 325:1010-1014.
Gonzales EB, Kawate T, and Gouaux E. (2009) Pore architecture and ion sites in acid-sensing ion channels and P2X receptors. Nature 460:599-604.
Kawate T, Michel JC, Birdsong WT, and Gouaux E. (2009) Crystal structure of the ATP-gated P2X(4) ion channel in the closed state. Nature 460:592-598.
Krishnamurthy H, Piscitelli CL and Gouaux E. (2009) Unlocking the molecular secrets of sodium-coupled transporters. Nature 459:347-355.
Singh SK, Piscitelli CL, Yamashita A and Gouaux E. (2008) A competitive inhibitor traps LeuT in an open-to-out conformation. Science 322:1655-1661.
Jasti J, Furukawa H, Gonzales EB and Gouaux E. (2007) Structure of acid-sensing ion channel 1 at 1.9 Å resolution. Nature 449:316-323.
Singh SK, Yamashita A and Gouaux E. (2007) Antidepressant binding site in a bacterial homologue of neurotransmitter transporters. Nature 448:952-956.
Boudker O, Ryan RM, Yernool D, Shimamoto K and Gouaux E. (2007) Coupling substrate and ion binding to extracellular gate of a sodium-dependent aspartate transporter. Nature 445:387-393.
Armstrong N, Jasti J, Beich-Frandsen M and Gouaux E. (2006) Measurement of conformational changes accompanying desensitization in an ionotropic glutamate receptor. Cell 127:85-97.
Yamashita A, Singh SK, Kawate T, Jin Y and Gouaux E. (2005) Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters. Nature 437:215-23.
Furukawa H, Singh SK, Mancusso R and Gouaux E. (2005) Subunit arrangement and function in NMDA receptors. Nature 438:185-92.