7QHB

Active state of GluA1/2 in complex with TARP gamma 8, L-glutamate and CTZ

7QHB の概要

• エントリーDOI: 10.2210/pdb7qhb/pdb
• 関連するPDBエントリー: 6QKC 7OCD
• EMDBエントリー: 13969
• 分子名称: Isoform Flip of Glutamate receptor 1, Isoform Flip of Glutamate receptor 2, Voltage-dependent calcium channel gamma-8 subunit, ... (8 entities in total)
• 機能のキーワード: glutamate, ampa receptor, tarps, membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 492706.75

構造登録者

Herguedas, B.,Kohegyi, B.,Zhang, D.,Greger, I.H. (登録日: 2021-12-11, 公開日: 2022-02-23, 最終更新日: 2024-11-13)

主引用文献

Herguedas, B.,Kohegyi, B.K.,Dohrke, J.N.,Watson, J.F.,Zhang, D.,Ho, H.,Shaikh, S.A.,Lape, R.,Krieger, J.M.,Greger, I.H.
Mechanisms underlying TARP modulation of the GluA1/2-gamma 8 AMPA receptor.
Nat Commun, 13:734-734, 2022

PubMed Abstract: AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory synapses in the brain. Glutamate binding to the receptor's ligand-binding domains (LBDs) leads to ion channel activation and desensitization. Gating kinetics shape synaptic transmission and are strongly modulated by transmembrane AMPAR regulatory proteins (TARPs) through currently incompletely resolved mechanisms. Here, electron cryo-microscopy structures of the GluA1/2 TARP-γ8 complex, in both open and desensitized states (at 3.5 Å), reveal state-selective engagement of the LBDs by the large TARP-γ8 loop ('β1'), elucidating how this TARP stabilizes specific gating states. We further show how TARPs alter channel rectification, by interacting with the pore helix of the selectivity filter. Lastly, we reveal that the Q/R-editing site couples the channel constriction at the filter entrance to the gate, and forms the major cation binding site in the conduction path. Our results provide a mechanistic framework of how TARPs modulate AMPAR gating and conductance.

PubMed: 35136046
DOI: 10.1038/s41467-022-28404-7

実験手法

ELECTRON MICROSCOPY (3.5 Å)