5VHW

GluA2-0xGSG1L bound to ZK

Summary for 5VHW

• Entry DOI: 10.2210/pdb5vhw/pdb
• Related: 5VHX 5VHY 5VHZ
• EMDB information: 8685
• Descriptor: Glutamate receptor 2,Germ cell-specific gene 1-like protein, {[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)-yl]methyl}phosphonic acid, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: ion channel, transport protein
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 4
• Total formula weight: 472406.69

Authors

Twomey, E.C.,Yelshanskaya, M.V.,Grassucci, R.A.,Frank, J.,Sobolevsky, A.I. (deposition date: 2017-04-13, release date: 2017-05-03, Last modification date: 2024-10-23)

Primary citation

Twomey, E.C.,Yelshanskaya, M.V.,Grassucci, R.A.,Frank, J.,Sobolevsky, A.I.
Structural Bases of Desensitization in AMPA Receptor-Auxiliary Subunit Complexes.
Neuron, 94:569-580.e5, 2017

PubMed Abstract: Fast excitatory neurotransmission is mediated by AMPA-subtype ionotropic glutamate receptors (AMPARs). AMPARs, localized at post-synaptic densities, are regulated by transmembrane auxiliary subunits that modulate AMPAR assembly, trafficking, gating, and pharmacology. Aberrancies in AMPAR-mediated signaling are associated with numerous neurological disorders. Here, we report cryo-EM structures of an AMPAR in complex with the auxiliary subunit GSG1L in the closed and desensitized states. GSG1L favors the AMPAR desensitized state, where channel closure is facilitated by profound structural rearrangements in the AMPAR extracellular domain, with ligand-binding domain dimers losing their local 2-fold rotational symmetry. Our structural and functional experiments suggest that AMPAR auxiliary subunits share a modular architecture and use a common transmembrane scaffold for distinct extracellular modules to differentially regulate AMPAR gating. By comparing the AMPAR-GSG1L complex structures, we map conformational changes accompanying AMPAR recovery from desensitization and reveal structural bases for regulation of synaptic transmission by auxiliary subunits.

PubMed: 28472657
DOI: 10.1016/j.neuron.2017.04.025

Experimental method

ELECTRON MICROSCOPY (7.8 Å)