8C2I

Transmembrane domain of resting state homomeric GluA1 AMPA receptor in complex with TARP gamma 3

8C2I の概要

• エントリーDOI: 10.2210/pdb8c2i/pdb
• EMDBエントリー: 16391
• 分子名称: Glutamate receptor 1 flip isoform, Voltage-dependent calcium channel gamma-3 subunit, PALMITIC ACID, ... (6 entities in total)
• 機能のキーワード: ampar, ion channels, neurotransmission, 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: 8
• 化学式量合計: 560921.51

構造登録者

Zhang, D.,Ivica, J.,Krieger, J.M.,Ho, H.,Yamashita, K.,Cais, O.,Greger, I. (登録日: 2022-12-22, 公開日: 2023-08-30, 最終更新日: 2024-10-23)

主引用文献

Zhang, D.,Ivica, J.,Krieger, J.M.,Ho, H.,Yamashita, K.,Stockwell, I.,Baradaran, R.,Cais, O.,Greger, I.H.
Structural mobility tunes signalling of the GluA1 AMPA glutamate receptor.
Nature, 621:877-882, 2023

PubMed Abstract: AMPA glutamate receptors (AMPARs), the primary mediators of excitatory neurotransmission in the brain, are either GluA2 subunit-containing and thus Ca-impermeable, or GluA2-lacking and Ca-permeable. Despite their prominent expression throughout interneurons and glia, their role in long-term potentiation and their involvement in a range of neuropathologies, structural information for GluA2-lacking receptors is currently absent. Here we determine and characterize cryo-electron microscopy structures of the GluA1 homotetramer, fully occupied with TARPγ3 auxiliary subunits (GluA1/γ3). The gating core of both resting and open-state GluA1/γ3 closely resembles GluA2-containing receptors. However, the sequence-diverse N-terminal domains (NTDs) give rise to a highly mobile assembly, enabling domain swapping and subunit re-alignments in the ligand-binding domain tier that are pronounced in desensitized states. These transitions underlie the unique kinetic properties of GluA1. A GluA2 mutant (F231A) increasing NTD dynamics phenocopies this behaviour, and exhibits reduced synaptic responses, reflecting the anchoring function of the AMPAR NTD at the synapse. Together, this work underscores how the subunit-diverse NTDs determine subunit arrangement, gating properties and ultimately synaptic signalling efficiency among AMPAR subtypes.

PubMed: 37704721
DOI: 10.1038/s41586-023-06528-0

実験手法

ELECTRON MICROSCOPY (2.7 Å)