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Structure and different conformational states of native AMPA receptor complexes

Author

Listed:
  • Terunaga Nakagawa

    (Howard Hughes Medical Institute, Massachusetts Institute of Technology)

  • Yifan Cheng

    (Harvard Medical School)

  • Elizabeth Ramm

    (Howard Hughes Medical Institute, Massachusetts Institute of Technology)

  • Morgan Sheng

    (Howard Hughes Medical Institute, Massachusetts Institute of Technology)

  • Thomas Walz

    (Harvard Medical School)

Abstract

Ionotropic glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system1,2. Their modulation is believed to affect learning and memory, and their dysfunction has been implicated in the pathogenesis of neurological and psychiatric diseases1,2. Despite a wealth of functional data, little is known about the intact, three-dimensional structure of these ligand-gated ion channels. Here, we present the structure of native AMPA receptors (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; AMPA-Rs) purified from rat brain, as determined by single-particle electron microscopy. Unlike the homotetrameric recombinant GluR2 (ref. 3), the native heterotetrameric AMPA-R adopted various conformations, which reflect primarily a variable separation of the two dimeric extracellular amino-terminal domains. Members of the stargazin/TARP family of transmembrane proteins co-purified with AMPA-Rs and contributed to the density representing the transmembrane region of the complex. Glutamate and cyclothiazide markedly altered the conformational equilibrium of the channel complex, suggesting that desensitization is related to separation of the N-terminal domains. These data provide a glimpse of the conformational changes of an important ligand-gated ion channel of the brain.

Suggested Citation

  • Terunaga Nakagawa & Yifan Cheng & Elizabeth Ramm & Morgan Sheng & Thomas Walz, 2005. "Structure and different conformational states of native AMPA receptor complexes," Nature, Nature, vol. 433(7025), pages 545-549, February.
  • Handle: RePEc:nat:nature:v:433:y:2005:i:7025:d:10.1038_nature03328
    DOI: 10.1038/nature03328
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    Cited by:

    1. Marc P. Forrest & Marc Dos Santos & Nicolas H. Piguel & Yi-Zhi Wang & Nicole A. Hawkins & Vikram A. Bagchi & Leonardo E. Dionisio & Sehyoun Yoon & Dina Simkin & Maria Dolores Martin-de-Saavedra & Ruoq, 2023. "Rescue of neuropsychiatric phenotypes in a mouse model of 16p11.2 duplication syndrome by genetic correction of an epilepsy network hub," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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