CCeMMP Seminar Series – Dr. Beatriz Herguedas June 2022

Structural studies of heteromeric AMPA Glutamate receptors

AMPA Glutamate Receptors (AMPARs) are ion channels located at post-synaptic neurons, where they mediate fast-excitatory neurotransmission. AMPARs are tetrameric receptors composed of different combinations of four subunits, GluA1 to GluA4, which also interact with auxiliary subunits, such as TARPs, cornichons or GSG1L. Here I will summarize the recent advances in the structural biology of AMPAR complexes, focusing on the gating cycle of the GluA1/2-TARP-g8 complex. I will describe the structural features of the receptor in different functional states and dissect the impact of TARP-g8 in the modulation of the channel properties. Combining structural data with electrophysiology and molecular dynamics simulations we show how TARP-g8 extracellular domains interact with the receptor ligand binding domain to modulate AMPAR function. We also analyze how receptor gating is coupled to changes in the selectivity filter, which determines cation selectivity, as well the role of TARP-g8 in the modulation of receptor rectification.

Dr. Beatriz Herguedas

“Ramón y Cajal” fellow

Institute for Biocomputation and Physics of Complex systems (BIFI)

University of Zaragoza (Spain)