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Structure and desensitization of AMPA receptor complexes with type II TARP γ5 and GSG1L.

Klykov O, Gangwar SP, Yelshanskaya MV, Yen L, Sobolevsky AI
Mol Cell 81 4771-4783.e7 (2021)
Related entries: 7ryy, 7ryz, 7rz5, 7rz6, 7rz7, 7rz8, 7rz9, 7rza

Cited: 10 times
EuropePMC logo PMID: 34678168

Abstract

AMPA receptors (AMPARs) mediate the majority of excitatory neurotransmission. Their surface expression, trafficking, gating, and pharmacology are regulated by auxiliary subunits. Of the two types of TARP auxiliary subunits, type I TARPs assume activating roles, while type II TARPs serve suppressive functions. We present cryo-EM structures of GluA2 AMPAR in complex with type II TARP γ5, which reduces steady-state currents, increases single-channel conductance, and slows recovery from desensitization. Regulation of AMPAR function depends on its ligand-binding domain (LBD) interaction with the γ5 head domain. GluA2-γ5 complex shows maximum stoichiometry of two TARPs per AMPAR tetramer, being different from type I TARPs but reminiscent of the auxiliary subunit GSG1L. Desensitization of both GluA2-GSG1L and GluA2-γ5 complexes is accompanied by rupture of LBD dimer interface, while GluA2-γ5 but not GluA2-GSG1L LBD dimers remain two-fold symmetric. Different structural architectures and desensitization mechanisms of complexes with auxiliary subunits endow AMPARs with broad functional capabilities.

Articles - 7rz4 mentioned but not cited (1)

  1. Structure and desensitization of AMPA receptor complexes with type II TARP γ5 and GSG1L. Klykov O, Gangwar SP, Yelshanskaya MV, Yen L, Sobolevsky AI. Mol Cell 81 4771-4783.e7 (2021)


Reviews citing this publication (1)

  1. Tetraspanins as Potential Modulators of Glutamatergic Synaptic Function. Becic A, Leifeld J, Shaukat J, Hollmann M. Front Mol Neurosci 14 801882 (2021)

Articles citing this publication (8)

  1. Conformational trajectory of allosteric gating of the human cone photoreceptor cyclic nucleotide-gated channel. Hu Z, Zheng X, Yang J. Nat Commun 14 4284 (2023)
  2. Differential regulation of tetramerization of the AMPA receptor glutamate-gated ion channel by auxiliary subunits. Certain N, Gan Q, Bennett J, Hsieh H, Wollmuth LP. J Biol Chem 299 105227 (2023)
  3. GSG1L-containing AMPA receptor complexes are defined by their spatiotemporal expression, native interactome and allosteric sites. Perozzo AM, Schwenk J, Kamalova A, Nakagawa T, Fakler B, Bowie D. Nat Commun 14 6799 (2023)
  4. Gating intermediates reveal inhibitory role of the voltage sensor in a cyclic nucleotide-modulated ion channel. Gao X, Schmidpeter PAM, Berka V, Durham RJ, Fan C, Jayaraman V, Nimigean CM. Nat Commun 13 6919 (2022)
  5. GluR2Q and GluR2R AMPA Subunits are not Targets of lypd2 Interaction. Lauriello A, McVeigh Q, Sung RJ. PLoS One 17 e0278278 (2022)
  6. Modulation of GluA2-γ5 synaptic complex desensitization, polyamine block and antiepileptic perampanel inhibition by auxiliary subunit cornichon-2. Gangwar SP, Yen LY, Yelshanskaya MV, Korman A, Jones DR, Sobolevsky AI. Nat Struct Mol Biol 30 1481-1494 (2023)
  7. Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics. Zhang D, Lape R, Shaikh SA, Kohegyi BK, Watson JF, Cais O, Nakagawa T, Greger IH. Nat Commun 14 1659 (2023)
  8. Opening of glutamate receptor channel to subconductance levels. Yelshanskaya MV, Patel DS, Kottke CM, Kurnikova MG, Sobolevsky AI. Nature 605 172-178 (2022)


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