Scientists in the Gouaux Lab have for the first time revealed the molecular structure of three major AMPA receptor–auxiliary subunit complexes in the hippocampus to near-atomic detail.

AMPA receptors — a subfamily of ionotropic glutamate receptors — play particularly important roles in the glutamatergic synapses of the hippocampus, the seat of memory and learning in the brain. However, the receptors do not function in isolation; they co-assemble with integral membrane proteins to form AMPA receptor–auxiliary subunit complexes. For more than 20 years, studies of these AMPAR complexes relied on engineered protein constructs of the receptor.

By developing and applying new monoclonal antibody reagents, researchers in the Gouaux lab successfully isolated the actual AMPA receptor and its complex of surrounding subunits from mouse hippocampi and imaged the samples using cryo-electron microscopy. Their technique for isolating the molecules has the potential to transform structural biology, opening the door for structure-based development of drugs to treat epilepsy and other seizure disorders.

The findings were published online May 12 in the journal Nature. Gouaux lab members Jie Yu, Ph.D. and Prashant Rao are first co-authors.