Abstract
Membrane proteins comprise only 1.8% of the atomic-resolution structures deposited in the RSB Protein Data Bank (http://pdbtm.enzim.hu). One bottleneck contributing to the under-representation of membrane protein structures is the requirement of a membrane mimic, such as a detergent micelle, to solubilize the membrane protein and form a stable protein-detergent complex (PDC). The mimic that leads to a structure is typically determined by empirically and exhaustively screening commercially available detergents. Understanding the relationship between detergent micelle physical properties and the stability, fold, and function of membrane proteins in PDC's reduces the extent of empirical screening required. Additionally, many structures are determined in detergent mixtures and with additives that affect the micelle properties and the protein-detergent complex. The aim of this study is to investigate micelle physical properties, both pure and mixed, and with additives commonly used in structural biology such as polyethylene glycols and cholesterol. In particular, we will present the thermodynamic properties of micelle formation (using isothermal titration calorimetry) and micelle size and shape (using small angle x-ray scattering) of binary detergent mixtures, as well as with additives. We will also present preliminary NMR data of membrane proteins in the characterized detergent micelles in order to investigate trends of detergent properties that correlate with stabilization of a protein fold. These results provide a foundation for understanding the role of detergents in membrane protein structure determination.
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