7RYZ

Structure of the complex of LBD-TMD part of AMPA receptor GluA2 with auxiliary subunit GSG1L bound to agonist quisqualate

Summary for 7RYZ

• Entry DOI: 10.2210/pdb7ryz/pdb
• EMDB information: 24749
• Descriptor: Glutamate receptor 2, (S)-2-AMINO-3-(3,5-DIOXO-[1,2,4]OXADIAZOLIDIN-2-YL)-PROPIONIC ACID (2 entities in total)
• Functional Keywords: ampa receptor, ion channel, neurotransmission, synapse, gsg1l, membrane protein
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 4
• Total formula weight: 516034.91

Authors

Gangwar, S.P.,Klykov, O.V.,Yelshanskaya, M.V.,Sobolevsky, A.I. (deposition date: 2021-08-26, release date: 2021-10-27, Last modification date: 2022-02-16)

Primary citation

Klykov, O.,Gangwar, S.P.,Yelshanskaya, M.V.,Yen, L.,Sobolevsky, A.I.
Structure and desensitization of AMPA receptor complexes with type II TARP gamma 5 and GSG1L.
Mol.Cell, 81:4771-4783.e7, 2021

PubMed Abstract: AMPA receptors (AMPARs) mediate the majority of excitatory neurotransmission. Their surface expression, trafficking, gating, and pharmacology are regulated by auxiliary subunits. Of the two types of TARP auxiliary subunits, type I TARPs assume activating roles, while type II TARPs serve suppressive functions. We present cryo-EM structures of GluA2 AMPAR in complex with type II TARP γ5, which reduces steady-state currents, increases single-channel conductance, and slows recovery from desensitization. Regulation of AMPAR function depends on its ligand-binding domain (LBD) interaction with the γ5 head domain. GluA2-γ5 complex shows maximum stoichiometry of two TARPs per AMPAR tetramer, being different from type I TARPs but reminiscent of the auxiliary subunit GSG1L. Desensitization of both GluA2-GSG1L and GluA2-γ5 complexes is accompanied by rupture of LBD dimer interface, while GluA2-γ5 but not GluA2-GSG1L LBD dimers remain two-fold symmetric. Different structural architectures and desensitization mechanisms of complexes with auxiliary subunits endow AMPARs with broad functional capabilities.

PubMed: 34678168
DOI: 10.1016/j.molcel.2021.09.030

Experimental method

ELECTRON MICROSCOPY (4.15 Å)