Architecture, Activation, and Conformational Plasticity in the GluA4 AMPA Receptor.

ABSTRACT: AMPA-subtype glutamate receptors (AMPARs), composed of subunits GluA1-4, mediate fast, excitatory synaptic transmission in the brain. After glutamate binding, AMPAR ion channels exhibit multiple subconductance states that tune neuronal responses to glutamate. GluA4 is the rarest subunit in the brain but is enriched in interneurons. Rising evidence points to the role of GluA4 AMPARs in the development of neurological diseases, but the structural mechanisms of GluA4 function have remained enigmatic. Here, from bilayer recordings and cryo-electron microscopy (cryo-EM), we report the unique features of GluA4 AMPARs that tune receptor function. We find that GluA4 AMPARs have a canonical "Y" shaped architecture where local dimer pairs are domain-swapped between the amino terminal domain (ATD) an

SUBMITTER: Hale WD 

PROVIDER: S-EPMC12262495 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature