How Cryo-EM is revolutionizing structural biology complexes after the "resolution revolution"
In 2017 R. Henderson, J.Frank and J Dubochet have been awarded the Nobel prize in Chemistry for having pioneered cryo electron microscopy (Cryo-EM) and Single Particle Analysis (SPA).
During the last few years Cryo-EM and SPA have grown to form technique to produce low-resolution structures of protein complexes (aka biology) to tools capable of achieving atomic and quasi-atomic resolution for complexes that nobody could solve with any other technique.
This incredible leap moves forward into
adoption of new techniques, Microcrystal Electron Diffraction (MicroED).
MicroED enables study of three-dimensional crystals a billion times smaller
than volumes used for x-ray crystallography. MicroED method is used to
determine high-resolution protein structures in a Cryo-Electron Microscope
(Cryo-EM) which sheds new light on chemical synthesis and small molecule
chemistry, and reveal unprecedented levels of detail in subatomic resolutions.
Cryo-EM has proved to be a very useful technique to be integrated with X-ray
and NMR for structure-based drug design. Cryo-EM benefit of specific
advantages:
• Basics of MicroED from concept to data collection, analysis and structure
determination.
• Crystallization or isotopic labelling is not needed.
• Amount of sample required is two orders of magnitude lower.
• Different functional conformation of a complex may be sorted out.
So it is no surprise that many structural biology groups all over the world are
seeking access to this technology in order to find answers to their most
relevant biological questions. Nevertheless most new comers to the field are
struggling to overcome the adoption barrier that this technique may pose in
term of: sample preparation and screening, automatic data acquisition and
progressive users training.
In this presentation we will see how the fast pace of cryo-EM growth is going to change the structural biology landscape for the best.
In particular we will discuss the
• The new development of MED (Micro electron Diffraction): a technology that
holds the promise to solve at high resolution, structures of nano-crystals .
And at 0.1% of the cost of an XFEL
• Cryo-TEM: Glacios, a 200kV X-FEG autoloader-provided system capable of
automatic screening of multiple grids and reduced footprint; Krios G3i: latest
Krios version with improved automation, increased cryo-performance and higher
throughput.