Solution Structure of an Intramembrane Aspartyl Protease via Small Angle Neutron Scattering.

摘要: Intramembrane aspartyl proteases (IAPs) comprise one of four families integral membrane that hydrolyze substrates within the hydrophobic lipid bilayer. IAPs include signal peptide peptidase, which processes remnant peptides from nascent polypeptides in endoplasmic reticulum, and presenilin, catalytic component γ-secretase complex Notch amyloid precursor protein. Despite their broad biomedical reach, basic structure-function relationships remain active areas research. Characterization membrane-bound proteins is notoriously challenging due to inherently character. For IAPs, oligomerization state solution outstanding question, with previous proposals for monomer, dimer, tetramer, octamer. Here we used small angle neutron scattering (SANS) characterize n-dodecyl-β-D-maltopyranoside (DDM) detergent solutions containing absent a microbial IAP ortholog. A unique feature SANS ability modulate solvent composition mask all but enzyme interest. The was enhanced by deuteration and, uniquely, DDM buffers were matched use both tail-deuterated D2O. radius gyration calculated corresponding ab initio consensus model are consistent monomer. slightly smaller than crystallographic suggesting more compact protein compared crystal lattice. Our study provides direct insight into oligomeric purified surfactant solution, demonstrates utility fully contrast-matching other intramembrane substrates.