CryoEM Seminar @ITQB NOVA - Misha Kudryashev

Structure of ion channels in membranes by cryo-EM

Webinar 

Dr. Misha Kudryashev

Max Planck Institute for Biophysics, Frankfurt on Main, Germany

email: misha.kudryashev@biophys.mpg.de
twitter: @kudryashev_lab

Ion channels open and close ion-conductive pores in membranes regulating many important physiological processes including synaptic transmission and propagation of action potentials. Native lipids, transmembrane gradients, interacting partners modulate structure and function of ion channels in physiological settings and are often lost during the preparation of the channels for structural analysis. The established and the developing methods of cryo electron microscopy allow gaining unique insights into regulation of membrane proteins by lipids. During the talk I will present structures and insights into activation of two ion channels in presence of native lipids:

(1) A serotonin receptor ion channel important for the functioning of nervous system reconstituted in lipid-containing nanoparticles and solved by single particle cryo electron microscopy. Interestingly, the structures are significantly different to the ones reported previously in detergent show ordered functionally important lipids.

(2) A giant calcium channel ryanodine receptor RyR1 involved in excitation-contraction in muscle in solved in native membranes using cryo electron tomography. The structures show non-trivial interplay between lipids and protein function.

Finally, I will discuss further perspective on mechanistic understanding of ion channel structure and function with the focus on preserving native context. Could we solve structures of membrane proteins in the future without protein purification?

Dr. Kudryashev is a Group Leader at the Max Planck Institute for Biophysics, and the Buchmann Institute for Molecular Life Sciences, Goethe University of Frankfurt, and a front-end leading scientist in the field of cryo-EM and cryo-ET (cryo-electron tomography).

His Group aims at understanding structure and regulation of medically important membrane proteins mostly from excitable cells, namely the effects that lipids, transmembrane gradients and native interacting partners have on activation of ion channels.

To experimentally determine defined conformations of ion channels, the Group employs membrane protein biochemistry, biophysics, cryo-EM and cryo-ET, as well as computer science.