Misha Kudryashev
Group Leader
Max Planck Institute of Biophysics &
Buchmann Institute for Molecular Life Sciences (BMLS)
Goethe University of Frankfurt
Max-von-Laue-Str. 3
60438 Frankfurt am Main, Germany
Phone +49 (0)69 6303-1700
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Figure 1. Structure of the mouse serotonin receptor in lipid vesicles [1].
A, B: Reconstituted receptors are imaged using EM (A) and low dose cryo electron tomography (B). Thousands of protein copies from B are mutually aligned and summed up resulting in a reconstruction at 12 Å resolution (C) where it is possible to fit the known high resolution structure (D). Scale bars: 50 nm in A, B and 5 nm in C.
For the structural analysis we use a multi-scale approach combining high resolution structural analysis with cryo electron tomography and subtomogram averaging [1]. While the recently revolutionized methods of single particle cryo-EM result in atomic resolution (3-4 Å) structures for a large number of proteins and protein complexes [2], it can be applied on the isolated proteins only. Subtomogram averaging may give information about more complex topologies but the resolution is limited to a roughly 10 Å. The major effort is to bring the resolution of subtomogram averaging higher by developing better data processing routines ourselves and in collaborations [3-5]. EM maps at 7 Å resolution in combination with knowing the atomic structure and computational methods give unprecedented insights into the gating of ion channels.