Distinct structural pathways coordinate the activation of ampa receptor-auxiliary subunit complexes

DOI: 10.1016/j.neuron.2016.01.038

Authors: G. b. Dawe (McGill University) , Maria Musgaard (University of Oxford) , Mark r. P. Aurousseau (McGill University) , Naushaba Nayeem (University of Liverpool) , Tim Green (University of Liverpool) , Philip C. Biggin (University of Oxford) , Derek Bowie (McGill University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Neuron , VOL 89 , PAGES 1264 - 1276

State: Published (Approved)
Published: March 2016

Abstract: Neurotransmitter-gated ion channels adopt different gating modes to fine-tune signaling at central synapses. At glutamatergic synapses, high and low activity of AMPA receptors (AMPARs) is observed when pore-forming subunits coassemble with or without auxiliary subunits, respectively. Whether a common structural pathway accounts for these different gating modes is unclear. Here, we identify two structural motifs that determine the time course of AMPAR channel activation. A network of electrostatic interactions at the apex of the AMPAR ligand-binding domain (LBD) is essential for gating by pore-forming subunits, whereas a conserved motif on the lower, D2 lobe of the LBD prolongs channel activity when auxiliary subunits are present. Accordingly, channel activity is almost entirely abolished by elimination of the electrostatic network but restored via auxiliary protein interactions at the D2 lobe. In summary, we propose that activation of native AMPAR complexes is coordinated by distinct structural pathways, favored by the association/dissociation of auxiliary subunits.

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography

Added On: 24/03/2016 10:40

Documents:
PIIS0896627316000635.pdf

Discipline Tags:

Health & Wellbeing Neurology Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)