X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor.

Nature
Alexander I SobolevskyEric Gouaux

Abstract

Ionotropic glutamate receptors mediate most excitatory neurotransmission in the central nervous system and function by opening a transmembrane ion channel upon binding of glutamate. Despite their crucial role in neurobiology, the architecture and atomic structure of an intact ionotropic glutamate receptor are unknown. Here we report the crystal structure of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-sensitive, homotetrameric, rat GluA2 receptor at 3.6 A resolution in complex with a competitive antagonist. The receptor harbours an overall axis of two-fold symmetry with the extracellular domains organized as pairs of local dimers and with the ion channel domain exhibiting four-fold symmetry. A symmetry mismatch between the extracellular and ion channel domains is mediated by two pairs of conformationally distinct subunits, A/C and B/D. Therefore, the stereochemical manner in which the A/C subunits are coupled to the ion channel gate is different from the B/D subunits. Guided by the GluA2 structure and site-directed cysteine mutagenesis, we suggest that GluN1 and GluN2A NMDA (N-methyl-d-aspartate) receptors have a similar architecture, with subunits arranged in a 1-2-1-2 pattern. We exploit the GluA2 stru...Continue Reading

References

Nov 7, 1991·Nature·K MoriyoshiS Nakanishi
Aug 3, 1990·Science·K KeinänenP H Seeburg
Apr 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S E Pedersen, J B Cohen
Apr 28, 1968·Journal of Molecular Biology·B W Matthews
Apr 1, 1995·Trends in Neurosciences·Z G Wo, R E Oswald
Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·Z G Wo, R E Oswald
Feb 12, 1998·Proceedings of the National Academy of Sciences of the United States of America·G Q Chen, E Gouaux
Jun 11, 1998·Science·C RosenmundC F Stevens
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·L TurskiE Ottow
Feb 1, 2000·Trends in Neurosciences·T R Soderling, V A Derkach
Oct 4, 2000·Nature Neuroscience·T C Smith, J R Howe
Mar 7, 2001·Cellular and Molecular Life Sciences : CMLS·T DresbachE D Gundelfinger
May 17, 2002·Nature·Yu SunEric Gouaux
Oct 24, 2002·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsThomas C Terwilliger
Dec 24, 2002·Trends in Neurosciences·Thomas KunerH Robert Guy
Feb 6, 2003·International Journal of Hematology·Shinpei Kasakura
Feb 28, 1959·Nature·D R CURTISJ C WATKINS
Feb 10, 2004·Neuron·Alexander I SobolevskyLonnie P Wollmuth
Feb 10, 2004·Neuron·Michelle S Horning, Mark L Mayer
Feb 24, 2004·Annual Review of Physiology·Mark L Mayer, Neali Armstrong
May 21, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Maria V YelshanskyLonnie P Wollmuth
May 28, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Rebecca Meier Klein, James R Howe
May 29, 2004·Trends in Neurosciences·Lonnie P Wollmuth, Alexander I Sobolevsky
Oct 16, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jeppe K ChristensenJuan Lerma

❮ Previous
Next ❯

Citations

Jul 28, 2012·The Journal of Membrane Biology·Coral Del ValAna-Nicoleta Bondar
Sep 3, 2013·European Biophysics Journal : EBJ·Timothy A CrossAnthony Watts
Apr 17, 2010·Pflügers Archiv : European journal of physiology·Diomedes E LogothetisRahul Mahajan
Jan 7, 2014·Pflügers Archiv : European journal of physiology·Guiscard SeebohmNathalie Strutz-Seebohm
May 5, 2011·Journal of Molecular Modeling·Hao-Jen Hsu, Wolfgang B Fischer
Apr 29, 2010·Current Neurology and Neuroscience Reports·Myrrhe van Spronsen, Casper C Hoogenraad
Mar 1, 2012·Journal of Molecular Neuroscience : MN·Juan ChengChen Zhang
Jul 27, 2012·Neuroscience Bulletin·Wei-Guang Li, Tian-Le Xu
Dec 26, 2013·Bioorganic & Medicinal Chemistry·Agnieszka A KaczorDariusz Matosiuk
Dec 3, 2013·European Journal of Pharmacology·Yuriy Pankratov, Ulyana Lalo
Mar 6, 2013·Insect Biochemistry and Molecular Biology·Raphael RytzRichard Benton
Oct 15, 2013·Journal of Pharmaceutical and Biomedical Analysis·Piotr DraczkowskiKrzysztof Jozwiak
Aug 17, 2011·Biochemistry·Oleg I BaryginDenis B Tikhonov
Apr 20, 2011·Journal of Chemical Information and Modeling·Pekka A PostilaOlli T Pentikäinen
May 28, 2013·Journal of Chemical Information and Modeling·Rafał D Urniaż, Krzysztof Jóźwiak
Feb 21, 2013·ACS Chemical Neuroscience·Walrati LimapichatDennis A Dougherty
Sep 20, 2012·Chemical Reviews·Damien LemoineThomas Grutter
Nov 6, 2012·Journal of Medicinal Chemistry·Sharan K BagalNigel A Swain
Dec 17, 2009·Nature·Lonnie P Wollmuth, Stephen F Traynelis
Jan 19, 2010·Nature Chemical Biology·James J Fleming, Pamela M England
Oct 29, 2010·Nature Communications·Praseeda MullasserilStephen F Traynelis
Apr 28, 2011·Nature Communications·Katie M VanceHiro Furukawa
Oct 13, 2011·Nature Communications·William F BorschelGabriela K Popescu
Apr 26, 2011·Nature Neuroscience·Anders S KristensenStephen F Traynelis
May 27, 2011·Nature Neuroscience·Victor Derkach
Jan 17, 2012·Nature Neuroscience·Beth Siegler RetchlessJon W Johnson
Mar 1, 2012·Nature Neuroscience·David J A Wyllie, Stephen F Traynelis
Feb 15, 2011·Nature Structural & Molecular Biology·Albert Y Lau, Benoît Roux
Mar 5, 2013·Nature Structural & Molecular Biology·Shujia ZhuPierre Paoletti
Jan 7, 2010·Nature Structural & Molecular Biology·Douglas L Theobald, Christopher Miller
Mar 5, 2011·Nature Structural & Molecular Biology·Mark L Mayer
Sep 22, 2010·Physical Chemistry Chemical Physics : PCCP·Ranjit VijayanPhilip C Biggin
May 12, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jennifer GonzalezVasanthi Jayaraman

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