Membrane-bound enzymes are notoriously challenging to study biochemically, and for most classes, basic structure-function questions remain unanswered. Membrane-bound enzymes require a lipid environment for function, which can be challenging to mimic in the lab. In this talk, I will show how my lab has used small angle neutron scattering (SANS) to better understand the organization of intramembrane aspartyl proteases (IAPs), integral membrane proteases that use aspartates to hydrolyze substrates within the water-depleted hydrophobic lipid bilayer, in different lipid-mimicking environments. I will describe how we used contrast matching of different components, as well as deuterating the IAP and selected other components, to isolate the signal of interest. Our studies provide new insight into the oligomerization of IAPs and connection to enzymatic properties. More broadly, a similar SANS approach with contrast matching could be useful for other membrane-bound protein and enzyme systems.
Raquel L. Lieberman (Sun,) studied this question.