6ud8 › Citations

Structures of the AMPA receptor in complex with its auxiliary subunit cornichon.

Nakagawa T
Science 366 1259-1263 (2019)
Related entries: 6peq, 6u5s, 6u6i, 6ucb, 6ud4

Cited: 37 times
EuropePMC logo PMID: 31806817

Abstract

In the brain, AMPA-type glutamate receptors (AMPARs) form complexes with their auxiliary subunits and mediate the majority of fast excitatory neurotransmission. Signals transduced by these complexes are critical for synaptic plasticity, learning, and memory. The two major categories of AMPAR auxiliary subunits are transmembrane AMPAR regulatory proteins (TARPs) and cornichon homologs (CNIHs); these subunits share little homology and play distinct roles in controlling ion channel gating and trafficking of AMPAR. Here, I report high-resolution cryo-electron microscopy structures of AMPAR in complex with CNIH3. Contrary to its predicted membrane topology, CNIH3 lacks an extracellular domain and instead contains four membrane-spanning helices. The protein-protein interaction interface that dictates channel modulation and the lipids surrounding the complex are revealed. These structures provide insights into the molecular mechanism for ion channel modulation and assembly of AMPAR/CNIH3 complexes.

Reviews - 6ud8 mentioned but not cited (1)

  1. AMPA receptor structure and auxiliary subunits. Kamalova A, Nakagawa T. J Physiol 599 453-469 (2021)


Reviews citing this publication (9)

  1. Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels. Hansen KB, Wollmuth LP, Bowie D, Furukawa H, Menniti FS, Sobolevsky AI, Swanson GT, Swanger SA, Greger IH, Nakagawa T, McBain CJ, Jayaraman V, Low CM, Dell'Acqua ML, Diamond JS, Camp CR, Perszyk RE, Yuan H, Traynelis SF. Pharmacol Rev 73 298-487 (2021)
  2. Cryo-EM as a powerful tool for drug discovery. Van Drie JH, Tong L. Bioorg Med Chem Lett 30 127524 (2020)
  3. Targeting receptor complexes: a new dimension in drug discovery. Rosenbaum MI, Clemmensen LS, Bredt DS, Bettler B, Strømgaard K. Nat Rev Drug Discov 19 884-901 (2020)
  4. Looking for Novelty in an "Old" Receptor: Recent Advances Toward Our Understanding of GABAARs and Their Implications in Receptor Pharmacology. Castellano D, Shepard RD, Lu W. Front Neurosci 14 616298 (2020)
  5. The Role of AMPARs Composition and Trafficking in Synaptic Plasticity and Diseases. Wu QL, Gao Y, Li JT, Ma WY, Chen NH. Cell Mol Neurobiol 42 2489-2504 (2022)
  6. Tetraspanins as Potential Modulators of Glutamatergic Synaptic Function. Becic A, Leifeld J, Shaukat J, Hollmann M. Front Mol Neurosci 14 801882 (2021)
  7. Interplay between Gating and Block of Ligand-Gated Ion Channels. Phillips MB, Nigam A, Johnson JW. Brain Sci 10 E928 (2020)
  8. Tuning synaptic strength by regulation of AMPA glutamate receptor localization. Stockwell I, Watson JF, Greger IH. Bioessays 46 e2400006 (2024)
  9. Structural dynamics in α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor gating. Gonzalez CU, Jayaraman V. Curr Opin Struct Biol 87 102833 (2024)

Articles citing this publication (27)



Quick links