Monday, November 25, 2013

X-ray laser protein modeling may be useful for solving membrane protein structures

Membrane proteins, such as G-protein coupled receptors and receptor tyrosine kinases, are well characterized for their role in important cellular functions and represent the major targets for new drug development. However, only a small fraction of membrane proteins have had their three dimensional structure completely mapped by traditional techniques. This lack of structural information is due, in large part, to the inability to obtain large crystals of pure membrane proteins.

Now, a recent article in Science explains an approach that does not require macroscopic crystals and can generate a 3-D structure without prior structural knowledge. The results of a collaboration between German and U.S. scientist are reported in the article entitled: 'De novo protein crystal structure determination from X-ray free-electron laser data'. In this article, the authors describe an approach which uses nanometer to micrometer sized crystals which are in a complex with a lanthanide compound, in this case gadolinium.

Single Protein crystal of Lysozyme
Photographed by Mathias Klode

New technique does not require a macroscopic crystal such as this
As proof of principle, the scientists obtained the essential information to complete the structure of a well characterized protein, lysozyme. They found that the de novo structure obtained using this technique was equivalent to that previously determined. It is hoped that this new approach will enable the characterization of proteins that had previously been elusive, such as membrane proteins. With the new structural information, scientists will be able to better understand interactions of potential drug compounds, which should lead to more effective treatment options.