Activation and Desensitization Mechanism of AMPA Receptor-TARP Complex by Cryo-EM.

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 yielding a receptor complex with altered gating kinetics, pharmacology, and pore properties. Here, we elucidate structures of the 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 sculpt the ligand-binding domain gating ring, enhancing kainate potency and diminishing the ensemble of desensitized states. Tduanyu37s encircle the receptor ion channel, stabilizing M2 helices and pore loops, illustrating how Tduanyu37s 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.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}