Heavy atom-bearing tripod amphiphiles for the membrane protein study

Abstract

Solubilization and stabilization of membrane proteins are prerequisites for their structural study. These bio-macromolecules tend to undergo structural degradation once removed from the native membranes, necessitating the addition of detergent molecules to separate the hydrophobic portion of membrane proteins from an aqueous medium. The encapsulation of membrane proteins by detergent micelles often leads to protein denaturation and/or aggregation, presumably because of limitations in detergent properties. Here, we introduced a new TPA with a heavy atom, iodine, and found that it is superior to DDM, the most successful conventional detergent, and TPA-2, a previously described TPA with a branched diglucoside, in terms of protein solubilization and stabilization efficacy for a fragile multi-subunit superassembly. Along with these favorable properties, the presence of the heavy atom may enable us to use this agent as a useful tool for membrane protein crystallization.