TCBG Seminar

Resolving gating and allosteric modulation in ion channels through simulations and small-angle neutron scattering

Professor Erik Lindahl
Department of Biochemistry & Biophysics
Stockholm University
Solna, Sweden

Monday, April 25, 2022
3:00 pm (CT)
Hybrid webinar recording


Pentameric ligand-gated ion channels (pLGICs) perform electrochemical signal transduction in organisms ranging from bacteria to humans. In addition to their normal gating cycle, pLGICs are highly sensitive to allosteric modulation where small compounds such as barbiturates, benzodiazepines or alcohols influence the gating kinetics by binding in separate sites, either in the transmembrane or extracellular domain. Despite a wealth of new experimental structures, it has been challenging to understand the gating kinetics, in particular since the channels rapidly undergo transitions to a desensitized nonconducting state rapidly after opening. I will present our recent combined experimental and computational work on a number of prokaryotic and eukaryotic pLGICs from the team, and how we are trying to combine low-resolution experimental techniques such as SANS (small-angle neutron scattering) with simulations to model channels under realistic conditions. In addition, I will show how we have been able to resolve structures in all separate functional states, their state-specific interactions with lipids, and not least how we are beginning to understand the properties of the desensitized state.

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