BioSoft-Colloquium: "Combining small-angle scattering of neutrons and X-rays to determine the low-resolution structure of membrane proteins"
Prof. L. Arleth, Structural Biophysics, Niels Bohr Institute, Faculty of Science, University of Copenhagen, Denmark
- 10 Jun 2013 16:00
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 also the central target in the pharmaceutical industry. Unfortunately, very little is known about the structure of membrane proteins. This significantly limits structurally rationalized approaches to drug development. So while protein crystallographers have had tremendous success in establishing knowledge about the structure of water soluble proteins down to atomic resolution to an extent that, at present, the Protein Data bank exhibits around 75.000 known protein structures, only ~300 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 membrane proteins are extremely difficult to crystallize. Hence, there is a demand for methods alternative to protein crystallography to provide structural information about this important class of proteins.
A central research activity of my research group at University of Copenhagen is to develop a general 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 nanoscale sample holder for the membrane proteins and by combining SAXS and contrast variation SANS, we try to determine the structure of a general membrane protein as well as the surrounding lipid membrane environment. In my talk, I will describe the results obtained in the project and discuss the challenges associated with our experimental strategy.
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