Using phospholipid nanodiscs as a platform for Small-Angle Scattering based structural studies of membrane proteins

Lise Arleth (University of Copenhagen, Denmark)

Membrane proteins are vital for the regulation of biological cell-function as well as in the communication between cells and about 25% of the proteins coded by the human genome are membrane proteins. Consequently, this class of proteins is a central target in the pharmaceutical industry. Despite remarkable breakthroughs in the last few years, little is still known about the structure of membrane proteins and their interaction with the local membrane environment. In the last decades, protein crystallographers have had tremendous success in establishing structural knowledge about water soluble proteins down to atomic resolution. This means that, while at present, the Protein Data bank exhibits around 75.000 known protein structures, only a few hundred of these correspond to unique membrane protein structures. The commonly accepted explanation for this lack of knowledge about the structure of membrane proteins is that they are extremely difficult to crystallize. This leads to a demand for methods alternative to protein crystallography to provide structural information about this important class of proteins and their local membrane environment. A central research activity of my research group at University of Copenhagen is to develop a platform for determining the low-resolution structure of membrane proteins based on combined Small-Angle Neutron Scattering (SANS) and Small-Angle X-ray Scattering (SAXS). We use the so-called Nanodisc-system as a sample holder for the single membrane proteins and by combining SAXS and contrast variation SANS, we aim for a method that allows us to determine the structure of a general membrane protein as well as the surrounding lipid membrane environment. In my talk, I will describe our very recent results obtained on the structure, localization and orientation of bacterio-rhodopsin incorporated into nanodics. The challenges associated with our experimental strategy as well the perspectives and limitations of the technique will be discussed.

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