Tuning Micelle Dimensions and Properties for Stabilizing Membrane Protein Fold and Function

Abstract

One major bottleneck to the investigation of membrane proteins is the stabilization of structure and function in detergents and lipid bilayers after purification from the native membrane. Detergents are the most successful membrane mimic, thus far, for NMR and X-ray crystallography structure determination of membrane proteins. However, the current empirical screening of detergents that stabilize protein function and fold is laborious, costly, and often is not successful. To better understand the physical determinants that stabilize a protein-detergent complex, we have systematically investigated the properties of detergent micelles. Specifically, we have determined that binary detergent mixtures form ideally mixed micelles and that many physical properties are different from the pure individual micelles and vary linearly with micelle mole fraction. The predictability of the shape, size, and surface properties of binary mixtures expands the molecular toolkit for applications that utilize detergents and provide a means to systematically test the influence these properties have on membrane protein fold and function. Our progress towards correlating detergent micelle physical properties with membrane protein structure and function will be presented.