Cryo-EM and 2D crystallography.

 "A picture shows me at a glance what it takes dozens of pages of a book to expound."
Ivan Turgenev wrote in Fathers and Sons (1862).

We all love to see illustrations in books and in magazines. The WWW had also push for images (and video) to be extensively used not quite replacing typing but, with 140 limits, a single pic can go great lenghts.

In biological sciences we depend very much on what we can "see". For example a lot of work on microbiology and cell biology is based on some kind of imaging. Maybe light microscopy, confocal microscopy or plain colony observation on a petri dish. And this can be extended beyond results. The is a journal devoted to biological research on video format:

"Journal of Visualized Experiments (JoVE) is a peer reviewed, PubMed indexed journal devoted to the publication of biological research in a video format."

Electron microscopy is the same league as (light) microscopy, ie. we strive to get good images to recover as much information as possible. In the case of single particle analysis and 2D crystallography the information we want to retrieve is 3D structure.  With single particle analysis is fairly straight forward to reach resolutions of 10 to 6 angstroms. 2D crystallography allows or < 2 angstroms. 


Now, I have nothing against X-ray diffraction for 3D structure solving. In fact, as the authors of "Coupling electron cryomicroscopy and X-ray crystallography to understand secondary active transport" point out, they complement each other nicely. If you care about reading the review I'll just spoil it a little here:


Membrane proteins are a challenge both as structure target as a biochemistry research target. Their very nature (membrane embedded, highly hydrophobic) makes them so. An definitive advantage of 2D crystallography is the presence of lipids for these membrane proteins. 

My favorite example on how this is advantageous is the example of NhaA. For this Sodium/Proton antiporter 2D crystals allowed the dissection of the pH activation and the substrate transport.  


A draw back of 2D crystallization is its current low throughput (when comparad to X-ray diff) but the gap will certainly will close during the current decade. Hopefully. But in the meantime, we will keep taking pictures and recovering high frequency info.



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