Understanding membrane protein-detergent interactions

One major obstacle to membrane protein structure determination is the selection of a detergent micelle that mimics the native lipid bilayer. Currently, detergents are selected by exhaustive screening because the effects of protein-detergent interactions on protein structure are poorly understood. Unlike lipids which form a bilayer, detergents form micelles. Micelles have different shapes and sizes depending on the detergent chemical structure. For NMR structural investigations, a multitude of detergents is screened until a condition that provides high quality NMR spectra is found. However, a correlation between the physical properties of the detergent micelle and the likelihood of obtaining a membrane protein structure is not known. The Columbus group is interested in studying how detergent – protein interactions modulate structure and dynamics and, therefore, structure determination of membrane proteins.

Determining the critical micelle concentration (cmc), size, and shape of detergent micelles
The physical properties of detergents determine the cmc, size, and shape of the micelles they form. In addition, proteins and additives may change the micelle properties. The Columbus laboratory uses small angle X-ray scattering (SAXS) to determine the size and shape of micelles and isothermal titration calorimetry (ITC) for cmc measurements in a variety of conditions that are relevant to membrane protein structure determination. In addition, we have begun to investigate mixtures of detergents in order to explore micelle sizes and shapes not sampled by pure detergents.
— Ryan Oliver

Determining the influence detergent properties have on the function and structure of membrane proteins
pdc.jpgCurrently, there is a lack of theory or understanding that allows detergents to be selected for membrane protein studies. To begin to understand the physical properties that are important in protein – interactions that maintain protein function and structure, the Columbus laboratory is systematically investigating several membrane proteins that differ in secondary structure and size in a variety of detergents.
— Ashton Brock and Shelby Lipes