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TitleActivation and Desensitization Mechanism of AMPA Receptor-TARP Complex by Cryo-EM.
Journal, issue, pagesCell, Vol. 170, Issue 6, Page 1234-1246.e14, Year 2017
Publish dateSep 7, 2017
AuthorsShanshuang Chen / Yan Zhao / Yuhang Wang / Mrinal Shekhar / Emad Tajkhorshid / Eric Gouaux /
PubMed AbstractAMPA receptors mediate fast excitatory neurotransmission in the mammalian brain and transduce the binding of presynaptically released glutamate to the opening of a transmembrane cation channel. ...AMPA receptors mediate fast excitatory neurotransmission in the mammalian brain and transduce the binding of presynaptically released glutamate to the opening of a transmembrane cation channel. Within the postsynaptic density, however, AMPA receptors coassemble with transmembrane AMPA receptor regulatory proteins (TARPs), yielding a receptor complex with altered gating kinetics, pharmacology, and pore properties. Here, we elucidate structures of the GluA2-TARP γ2 complex in the presence of the partial agonist kainate or the full agonist quisqualate together with a positive allosteric modulator or with quisqualate alone. We show how TARPs sculpt the ligand-binding domain gating ring, enhancing kainate potency and diminishing the ensemble of desensitized states. TARPs encircle the receptor ion channel, stabilizing M2 helices and pore loops, illustrating how TARPs alter receptor pore properties. Structural and computational analysis suggests the full agonist and modulator complex harbors an ion-permeable channel gate, providing the first view of an activated AMPA receptor.
External linksCell / PubMed:28823560 / PubMed Central
MethodsEM (single particle)
Resolution4.9 - 7.7 Å
Structure data

EMDB-8721, PDB-5vot:
Structure of AMPA receptor-TARP complex
Method: EM (single particle) / Resolution: 4.9 Å

EMDB-8722, PDB-5vou:
Structure of AMPA receptor-TARP complex
Method: EM (single particle) / Resolution: 6.4 Å

EMDB-8723, PDB-5vov:
Structure of AMPA receptor-TARP complex
Method: EM (single particle) / Resolution: 7.7 Å

Source
  • rattus norvegicus (Norway rat)
Keywordsmembrane protein / metal transport / AMPA receptor-TARP complex / TARP modulation mechanism / partially open channel gate. / partial agonist bound. / full agonist bound / desensitized ensemble.

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