New opportunities come in the new year.
Higher standards have been on our menu for many years.

We usually take a break from our monthly newsletter in January to ramp up for the New Year, but sometimes there is a result so huge, that it deserves to be shared.  And by huge, we mean 1.6 MDa huge!

Published on December 14th in Nature Communications, the lab of Doryen Bubeck at Imperial College London determined the structures of both the open (PDB: 6H03) and closed (PDB: 6H04) conformations of the multiprotein Membrane Attack Complex
(MAC)(1).  Made up of 24 polypeptide chains (C5b, C6, C7, C8α, C8β, C8γ, and 18 x C9), MAC is a component of the innate immune response, and is able to disrupt the cell membrane of pathogens such as, Gram-negative bacteria, viruses, and parasites, leading to cell death(2).  Each of the individual components of MAC assemble on the cell membrane of the pathogen and form a 110 Å diameter transmembrane channel, killing the target cell.  The two structures determined in this study allow for the creation of a model of how MAC ruptures lipid bilayers, where the partially inserted pre-complex (C5b, C6, C7) lowers the activation energy needed for bending the bilayer.  Upon binding of C8α/β/γ to the complex, a nonlamellar edge is formed through bending and piercing the bilayer, which allows for subsequent assembly of the C9 monomers and pore formation.

In this study, the MAC complex was purified by forming liposomes comprised of DOPC and DOPE. Each of the purified individual complement proteins was added stepwise to the liposomes to form the MAC assembly. The MAC assembly was solubilized using 1.5% CYMAL-5 and 1 mg/ml DOPC.  After solubilization, the complexes were purified using density gradient centrifugation in a sucrose solution containing 0.004% CYMAL-7 Neopentyl Glycol.  To our knowledge, these represent the first deposited structures that used our CYMAL-7 Neopentyl Glycol detergent in the structure determination step.

DOPE is one of the recently added lipids to our continually expanding catalog along with DPPE, DPPG-Na, DOPS, and the LCP host lipid 7.7 MAG.  Our full catalog of phospholipids can be found here.

 
References:
  1. Menny, A, et al. (2018) Nat Commun. 9(1):5316, doi: 10.1038/s41467-018-07653-5.
  2. Serna, M, et al. (2016) Nat Commun. 7:10587, doi:10.1038/ncomms10587.