A fascinating look back can lead to
continuing higher standards ahead.

As we've done in previous years, we like to start each New Year by providing you with an overview of detergent usage in membrane protein structural biology from the previous year. You can check out our previous overviews at the following links: 2015 overview, 2016 overview, 2017 overview.

Using data from Steve White's "Membrane Proteins of Known 3D Structure" (1), we have been maintaining a database of all unique membrane protein structures, and the detergents used in their solubilization, purification and structure determination. 2018 was certainly a record-breaking year for membrane protein research with 107 unique membrane protein structures determined, bringing the overall total of unique structures to 853. Below, we'll share some interesting statistics about the detergent usage in these structures determined in 2018.

We are continuing to see the profound effect Cryo-EM is having on membrane protein structure determination. 2017 was the first year where the number of unique membrane protein structures determined by Cryo-EM (52%) was greater than X-ray crystallography (44%). Once again, this trend continues in 2018. Of the 107 unique membrane protein structures, 57 were determined by Cryo-EM, 48 by X-Ray crystallography, 1 by NMR, and 1 by Cryo-ET (Figure 1).

For membrane protein solubilization and purification, we observe similar trends as previous years. Once again DDM +/- CHS is the most commonly used detergent for the solubilization (55%), and purification (50%) of membrane proteins. Other commonly used detergents for membrane protein solubilization in 2018 were LMNG +/- CHS (13%), Digitonin (7%), DM (6%), Triton X-100 (4%), and DMNG (3%) (Figure 2). The results for membrane protein purification differ slightly, showing that the detergent used for solubilization is not always the best choice for purification. The other commonly used detergents for membrane protein purification in 2018 include Digitonin (13%), LMNG +/- CHS (10%), DM (8%), LDAO (6%), GDN (3%), and DMNG (3%) (Figure 3).

Lastly, we examined which detergents were most commonly used for the structure determination step. In total, over 25 different detergents were used, with the most common being DDM +/- CHS (27%), Digitonin (17%), LMNG +/- CHS (11%), Amphipols A8-35 and PMAL-C8 (8%), Lipid Nanodiscs (4%), C8E4 (4%), and GDN (3%) (Figure 4). As we observed last year, Digitonin, Amphipol A8-35, Amphipol PMAL-C8, Nanodiscs, and GDN were only used on structures determined by Cryo-EM. Likewise, the detergent C8E4 was only used on beta-barrel proteins determined by X-ray crystallography.

If you are interested in comparing trends in detergent usage and methods, have a look at our analysis from 2015, 2016, and 2017. Also, stay tuned, we'll have a very exciting announcement in a few months about making all of this detergent usage data available on our website as a publicly available database!


 References:
  1. Membrane Proteins of Known 3D Structure. Steven White Laboratory.  Accessed 01/14/2019: http://blanco.biomol.uci.edu/mpstruc/
 

 
 


 
 


 
 



 
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