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Structure paper

タイトル	Architecture of the heteromeric GluA1/2 AMPA receptor in complex with the auxiliary subunit TARP γ8.
ジャーナル・号・ページ	Science, Vol. 364, Issue 6438, Year 2019
掲載日	2019年4月26日
著者	Beatriz Herguedas / Jake F Watson / Hinze Ho / Ondrej Cais / Javier García-Nafría / Ingo H Greger /
PubMed 要旨	AMPA-type glutamate receptors (AMPARs) mediate excitatory neurotransmission and are central regulators of synaptic plasticity, a molecular mechanism underlying learning and memory. Although AMPARs ...AMPA-type glutamate receptors (AMPARs) mediate excitatory neurotransmission and are central regulators of synaptic plasticity, a molecular mechanism underlying learning and memory. Although AMPARs act predominantly as heteromers, structural studies have focused on homomeric assemblies. Here, we present a cryo-electron microscopy structure of the heteromeric GluA1/2 receptor associated with two transmembrane AMPAR regulatory protein (TARP) γ8 auxiliary subunits, the principal AMPAR complex at hippocampal synapses. Within the receptor, the core subunits arrange to give the GluA2 subunit dominant control of gating. This structure reveals the geometry of the Q/R site that controls calcium flux, suggests association of TARP-stabilized lipids, and demonstrates that the extracellular loop of γ8 modulates gating by selectively interacting with the GluA2 ligand-binding domain. Collectively, this structure provides a blueprint for deciphering the signal transduction mechanisms of synaptic AMPARs.
リンク	Science / PubMed:30872532 / PubMed Central
手法	EM (単粒子)
解像度	4.4 - 6.3 Å
構造データ	4572 6qkc EMDB-4572, PDB-6qkc: GluA1/2 In complex with auxiliary subunit gamma-8 手法: EM (単粒子) / 解像度: 4.4 Å 4575 6qkz EMDB-4575, PDB-6qkz: Full length GluA1/2-gamma8 complex 手法: EM (単粒子) / 解像度: 6.3 Å
化合物	ChemComp-E2Q: 6-nitro-2,3-bis(oxidanylidene)-1,4-dihydrobenzo[f]quinoxaline-7-sulfonamide / アンタゴニストYM / NBQX ChemComp-OLC: (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate / L-グリセロ-ル3-オレア-ト ChemComp-NAG*: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン
由来	rattus norvegicus (ドブネズミ)
キーワード	MEMBRANE PROTEIN (膜タンパク質) / AMPAR / ion channel (イオンチャネル) / GluA1 / GluA2 / tarp