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TitleArchitecture of the heteromeric GluA1/2 AMPA receptor in complex with the auxiliary subunit TARP γ8.
Journal, issue, pagesScience, Vol. 364, Issue 6438, Year 2019
Publish dateApr 26, 2019
AuthorsBeatriz Herguedas / Jake F Watson / Hinze Ho / Ondrej Cais / Javier García-Nafría / Ingo H Greger /
PubMed AbstractAMPA-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.
External linksScience / PubMed:30872532 / PubMed Central
MethodsEM (single particle)
Resolution4.4 - 6.3 Å
Structure data

4572

6qkc

EMDB-4572, PDB-6qkc:
GluA1/2 In complex with auxiliary subunit gamma-8
Method: EM (single particle) / Resolution: 4.4 Å

4575

6qkz

EMDB-4575, PDB-6qkz:
Full length GluA1/2-gamma8 complex
Method: EM (single particle) / Resolution: 6.3 Å

Chemicals

ChemComp-E2Q:
6-nitro-2,3-bis(oxidanylidene)-1,4-dihydrobenzo[f]quinoxaline-7-sulfonamide / antagonist*YM / NBQX

ChemComp-OLC:
(2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • rattus norvegicus (Norway rat)
KeywordsMEMBRANE PROTEIN / AMPAR / ion channel / GluA1 / GluA2 / tarp

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