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Architecture of the heteromeric GluA1/2 AMPA receptor in complex with the auxiliary subunit TARP γ8

DOI: 10.1126/science.aav9011 DOI Help

Authors: Beatriz Herguedas (MRC Laboratory of Molecular Biology) , Jake F. Watson (MRC Laboratory of Molecular Biology) , Hinze Ho (MRC Laboratory of Molecular Biology) , Ondrej Cais (MRC Laboratory of Molecular Biology) , Javier Garcia-nafria (MRC Laboratory of Molecular Biology) , Ingo H. Greger (MRC Laboratory of Molecular Biology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science

State: Published (Approved)
Published: March 2019
Diamond Proposal Number(s): 17434

Abstract: 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-EM structure of the heteromeric GluA1/2 receptor associated with two TARP γ8 auxiliary subunits, the principle 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 controlling 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.

Journal Keywords: AMPA glutamate receptor, synapse, cryoEM

Subject Areas: Biology and Bio-materials, Chemistry

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
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