Sometimes taking a quick look back
can help you achieve more in the future.

As we have done at the start of 2016 and 2017, we wanted to ring in 2018 by providing an overview of detergent usage in membrane protein structural biology from the previous year. Last year was an exciting year for membrane protein research, with a number of novel structures being published. This included the MRP1 multidrug resistance protein(1), the ABCA1 lipid exporter(2), the CLC chloride ion channel(3), the TRP channels TRPM4(4), TRPML1(5), TRPML3(6), and the first full length structure of a class B GPCR (and first Cryo-EM structure of a GPCR!)(7), to name a few.
 
Once again, using data from Steve White’s “Membrane Proteins of Known 3D Structure” database(8), we mined each publication of unique membrane protein structures deposited in 2017 to determine which detergents were used in the solubilization, purification, and structure determination of these proteins. In total, there were 63 unique membrane protein structures deposited in 2017, bringing the overall total of unique structures to 735. In this month’s newsletter, we’ll share the detergent usage data for the unique membrane protein structures published in 2017.
 
Of the 63 unique structures, 28 were determined by X-ray crystallography, 33 by Cryo-EM, 1 by LCP-SFX, and 1 by NMR (Figure 1). This is the first year where the number of unique membrane protein structures determined by Cryo-EM is greater than the structures determined by Cryo-EM. In 2015, Cryo-EM was the method used for 16% of the deposited unique membrane protein structures, while in 2016, Cryo-EM accounted for 21% of the structures. This trend is also seen when looking at all Cryo-EM structures (soluble and membrane protein) deposited in 2017, which accounted for 5% of all deposited structures (an increased of 36% compared to 2016)(9). This massive increase in the number of deposited structures determined by Cryo-EM is a testament to the utility of this method for protein structural biology.
 
We examined which detergents were used most frequently in the solubilization, purification, and structure determination of the unique membrane proteins deposited in 2017. As in previous years, DDM +/- CHS was used most frequently (52%) for the solubilization of membrane proteins (Figure 2). The other commonly used detergents for solubilization include LMNG +/- CHS (19%), and Digitonin (8%). Similar trends are observed for the detergents used in the purification (Figure 3), with the same detergents, DDM +/- CHS (46%), LMNG +/- CHS (17%), and Digitonin (14%) ranking in the top three.  Other detergents commonly used for purification include DM +/- CHS (5%), CYMAL-6 (3%), and LDAO (3%).
 
Lastly, we looked at which detergents were used for the structure determination step (Figure 4). In total, 19 different detergents were used for this step, with the top three once again being DDM +/- CHS (27%), Digitonin (14%), and LMNG +/- CHS (14%). The next two commonly used detergents include Amphipols (A8-35, PMAL-C8, and NAPol) (13%) and lipid nanodiscs (8%), which along with Digitonin, were only used in structures determined by Cryo-EM.
 
If you are interested in comparing trends in detergent usage from year to year, have a look at the analysis we did for structures published in 2015 and 2016. Find this data interesting? We’re getting close to making all of the detergent usage data for all 735 (and counting!) unique membrane protein strucutres available on our website as a publically available database.  Stay tuned!
 

 

     


 

References:
  1. Johnson, Z. L. and Chen, J., (2017) Cell 168(6), 1075-1085.
  2. Qian, H., et al. (2017) Cell 169(7), 1228-1239.
  3. Park, E., et al. (2017) Nature 541(7638), 500-505.
  4. Hirschi, M., et al. (2017) Nature 550(7676), 411-414.
  5. Chen, Q., et al. (2017) Nature 550(7676), 415-418.
  6. Winkler, P. A., et al. (2017) Nature 552(7684), 200-204.
  7. Liang, Y. L., et al. (2017) Nature 546(7656), 118-123.
  8. Membrane Proteins of Known 3D Structure. Steven White Laboratory.  Accessed 01/12/2018: http://blanco.biomol.uci.edu/mpstruc/
  9. RCSB Protein Data Bank.  Accessed 01/12/2018: http://www.rcsb.org/pdb/.
 

 
 


 
 


 
 



 
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