Modulation of GluA2–γ5 synaptic complex desensitization, polyamine block and antiepileptic perampanel inhibition by auxiliary subunit cornichon-2

• Published in: Nature structural & molecular biology Vol. 30; no. 10; pp. 1481 - 1494
• Main Authors: Gangwar, Shanti Pal, Yen, Laura Y., Yelshanskaya, Maria V., Korman, Aryeh, Jones, Drew R., Sobolevsky, Alexander I.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2023; Nature Publishing Group
• Subjects: 631/45/269/1149; 631/535/1258/1259; Animals; Anticonvulsants - pharmacology; Antiepileptic agents; Binding; Biochemistry; Biological Microscopy; Biomedical and Life Sciences; Channel gating; Desensitization; Electron microscopy; Epilepsy; Humans; Ion channels; Life Sciences; Medical treatment; Membrane Biology; Mental disorders; Mice; Neurological diseases; Neurotransmission; Nitriles; Open channels; Polyamines; Polyamines - pharmacology; Protein Structure; Rats; Receptor mechanisms; Receptors; Receptors, AMPA - chemistry; Receptors, AMPA - metabolism; Spermidine; Structure-function relationships; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors

Synaptic complexes of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) with auxiliary subunits mediate most excitatory neurotransmission and can be targeted to treat neuropsychiatric and neurological disorders, including epilepsy. Here we present cryogenic-electron micr...