Specific Lipid Binding of Membrane Proteins in Detergent Micelles Characterized by NMR and Molecular Dynamics

Many membrane proteinsbind specifically to lipids as an integral component of their structures. The ability of detergents to support lipid binding is thus an important consideration when solubilizing membrane proteinsfor structural studies. In particular, the zwitterionic phosphocholine(PC)-based detergents, which have been widely used in solution NMR studies of channels and transporters, are controversial because of their strong solubilizationpower and thus perceived as more denaturing than nonionic detergents such as the maltosides. Here, we investigate the ability of the mitochondrial ADP/ATP carrier (AAC) to specifically bind cardiolipin, a mitochondrial lipid important for the carrier function, in dodecylphosphocholine (DPC) micelles. We found that in DPC, the AAC specifically binds cardiolipinin a manner consistent with the bound cardiolipinsfound in the crystal structures of the AAC determined in n-decyl β-d- maltoside. Our results suggest that PC detergent is compatible with specific lipid bi...