Misha Kudryashev: Native structure and gating of ion channels

Guest Group – from August 2021 Misha Kudryashev moved to the Max Delbrück Center for Molecular Medicine in Berlin, Germany

In situ structural biology of membrane protein complexes

Our research aims at understanding structure and regulation of medically important membrane proteins mostly from excitable cells. We are particularly interested in the effects that lipids, transmembrane gradients and native interacting partners have on activation of ion channels. To experimentally determine the defined conformations of ion channels in my group we use membrane protein biochemistry, biophysics, cryo electron microscopy (cryo-EM) and tomography (cryo-ET) as well as computer science.

We use two structural methods as main tools: firstly, single particle cryo-EM to understand protein structure at near-atomic resolution in presence of lipids in the defined functional states (open, closed, deactivated). Secondly, in situ structural biology by cryo electron tomography and subtomogram averaging (StA), which enables structural analysis in native or native-like environment. While a few high-resolution structures have already been reported, the method is currently cumbersome and mostly results in structures with lower resolution. In order to turn subtomogram averaging into a broadly used structural biology technique we develop algorithmic tools and transparent software workflows providing significant boost in resolution.

We are primarily funded by the amazing Sofja Kovalevskaja Award from the Alexander von Humboldt Foundation. We further thank German Research Foundation (DFG) for a generous project grant. Fellowship programmes from: Chinese Student Council, Taiwaneese Government, Josef Buchmann Foundation, Max Planck International Graduate School (IMPRS), G-Max Precision. The group received funding from the state of Hessen two large research consortia: Collaborative Research Project on Membrane Transport (http://www.sfb807.de/) and Cluster of Excellence on Macromolecular Complexes (https://www.cef-mc.de/), both funded by DFG.

We are a multi-national multidisciplinary group working together to solve challenging basic problems related to membrane proteins. If you are interested to join us on a relatively long-term basis please write an email to misha.kudryashev(at)biophys.mpg.de and with a CV and a few words about your interests.

Selected Publications

DOI

Sanchez R.M., Zhang Y., Chen W., Dietrich L., Kudryashev M.

Subnanometer-resolution structure determination in situ by hybrid subtomogram averaging - single particle cryo-EM.

Nature Communications 11, 3709 (2020)

DOI

Chen W. and Kudryashev M.

Structure of RyR1 in Native Membranes

EMBO Rep. 2020 May 6; 21(5): e49891

DOI

Sánchez R.M., Mester R., Kudryashev M.

Fast Cross Correlation for Limited Angle Tomographic Data.

In: Felsberg M., Forssén PE., Sintorn IM., Unger J. (eds) Image Analysis. SCIA 2019.
Lecture Notes in Computer Science, Vol 11482. Springer

DOI

Kudryashev M., Castaño-Díez D., Deluz C., Hassaine G., Grasso L., Graf-Meyer A., Vogel H., Stahlberg H.

The Structure of the Mouse Serotonin 5-HT3 Receptor in Lipid Vesicles.

Structure 24: 165–70 (2016).

DOI

Kudryashev M., Wang R., Brackmann M., Scherer S., Maier T., Baker D., DiMaio F., Stahlberg H., Egelman E.H., Basler M.

The structure of the type six secretion system contractile sheath solved by cryo-electron microscopy.

Cell. 160:952-62 (2015)

DOI

Nans A., Kudryashev M., Saibil H.R., Hayward R.D.

Structure of a bacterial type III secretion system in contact with a host membrane in situ.

Nat. Commun. 6:10114 (2015)