5WEO

Activated GluA2 complex bound to glutamate, cyclothiazide, and STZ in digitonin

Summary for 5WEO

• Entry DOI: 10.2210/pdb5weo/pdb
• EMDB information: 8819 8820 8821 8822 8823
• Descriptor: Glutamate receptor 2,Voltage-dependent calcium channel gamma-2 subunit chimera, GLUTAMIC ACID, CYCLOTHIAZIDE (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: 464155.90

Authors

Twomey, E.C.,Yelshanskaya, M.V.,Grassucci, R.A.,Frank, J.,Sobolevsky, A.I. (deposition date: 2017-07-10, release date: 2017-08-02, Last modification date: 2024-10-23)

Primary citation

Twomey, E.C.,Yelshanskaya, M.V.,Grassucci, R.A.,Frank, J.,Sobolevsky, A.I.
Channel opening and gating mechanism in AMPA-subtype glutamate receptors.
Nature, 549:60-65, 2017

PubMed Abstract: AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-subtype ionotropic glutamate receptors mediate fast excitatory neurotransmission throughout the central nervous system. Gated by the neurotransmitter glutamate, AMPA receptors are critical for synaptic strength, and dysregulation of AMPA receptor-mediated signalling is linked to numerous neurological diseases. Here we use cryo-electron microscopy to solve the structures of AMPA receptor-auxiliary subunit complexes in the apo, antagonist- and agonist-bound states and determine the iris-like mechanism of ion channel opening. The ion channel selectivity filter is formed by the extended portions of the re-entrant M2 loops, while the helical portions of M2 contribute to extensive hydrophobic interfaces between AMPA receptor subunits in the ion channel. We show how the permeation pathway changes upon channel opening and identify conformational changes throughout the entire AMPA receptor that accompany activation and desensitization. Our findings provide a framework for understanding gating across the family of ionotropic glutamate receptors and the role of AMPA receptors in excitatory neurotransmission.

PubMed: 28737760
DOI: 10.1038/nature23479

Experimental method

ELECTRON MICROSCOPY (4.2 Å)