5VOU

Structure of AMPA receptor-TARP complex

Summary for 5VOU

• Entry DOI: 10.2210/pdb5vou/pdb
• Related: 5VOT 5VOV
• EMDB information: 8722
• Descriptor: Glutamate receptor 2, Voltage-dependent calcium channel gamma-2 subunit (2 entities in total)
• Functional Keywords: ampa receptor-tarp complex, tarp modulation mechanism, partial agonist bound., membrane protein, metal transport
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 8
• Total formula weight: 541876.55

Authors

Chen, S.,Zhao, Y.,Wang, Y.S.,Shekhar, M.,Tajkhorshid, E.,Gouaux, E. (deposition date: 2017-05-03, release date: 2017-07-12, Last modification date: 2019-12-18)

Primary citation

Chen, S.,Zhao, Y.,Wang, Y.,Shekhar, M.,Tajkhorshid, E.,Gouaux, E.
Activation and Desensitization Mechanism of AMPA Receptor-TARP Complex by Cryo-EM.
Cell, 170:1234-1246.e14, 2017

PubMed Abstract: 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.

PubMed: 28823560
DOI: 10.1016/j.cell.2017.07.045

Experimental method

ELECTRON MICROSCOPY (6.4 Å)