Superbright and fast x-rays image single layer of proteins

Thu, 02/13/2014 - 1:50pm

Caught by XFEL: X-ray free-electron lasers can create images (left) that accurately reflect the known structure of proteins determined by conventional methods (right), in this case, three bacteriorhodopsin proteins.In biology, a protein's shape is key to understanding how it causes disease or toxicity. Researchers who use x-rays to take snapshots of proteins need a billion copies of the same protein stacked and packed into a neat crystal. Now, scientists using exceptionally bright and fast x-rays can take a picture that rivals conventional methods with a sheet of proteins just one protein molecule thick.

Using a type of laser known as XFEL, the technique opens the door to learning the structural details of almost 25% of known proteins, many of which have been overlooked due to their inability to stack properly. The team of researchers led by the Department of Energy's Pacific Northwest and Lawrence Livermore National Laboratories report their results with this unique form of x-ray diffraction in the March issue of the International Union of Crystallography Journal.


Evans co-led the team of two dozen scientists with LLNL physicist Matthias Frank. The bright, fast X-rays were produced at the Linac Coherent Light Source at SLAC National Accelerator Laboratory in Menlo Park, Calif., the newest of DOE's major x-ray light source facilities at the national laboratories. LCLS, currently the world's most powerful x-ray laser, is an x-ray free-electron laser. It produces beams millions of times brighter than earlier x-ray light sources.



Not your family's crystal


But many proteins found in nature do not stack easily. Some jut from the fatty membranes that cover cells, detecting and interacting with other cells and objects, such as viruses or bacteria, in the surrounding area. These proteins are not used to having others of their kind stack on top. These so-called membrane proteins make up about 25% of all proteins but only 2% of proteins that researchers have determined structures for.

Wafer thin

Researchers in the last decade have been pursuing the idea that one sheet of proteins could be visualized if the x-rays were bright enough but flashed on and off quickly enough to limit the damage wrought by the powerful x-rays. Two years ago, scientists demonstrated they could use XFEL technology on crystals of proteins about 15 to 20 sheets thick.


The team shined the super-bright X-rays for a brief moment—about 30 femtosec, a few million billionths of a second—on the protein crystals. They created so much data in the process that it took them more than a year to analyze all of it.




Femtosecond X-ray Diffraction from Two-Dimensional Protein Crystals

Source: Pacific Northwest National Laboratory


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