Researchers have captured high-resolution images of simple lysozyme biomolecules using sophisticated X-ray crystallography technology.

An international team led by the US Department of Energy’s (DOE) SLAC National Accelerator Laboratory (Menlo Park, CA, USA) has proved how the world’s most powerful X-ray laser can assist in decoding the structures of biomolecules, and in the processes helped to forge vital new research paths in biology.

The researcher’s experiments, reported online May 31, 2012, in Science, used SLAC’s linac coherent light source (LCLS) to capture ultra-high-resolution views of crystallized biomolecules, including a small protein found in egg whites called lysozyme. For many years, scientists have reconstructed the shape of biologic molecules and proteins by illuminating crystallized samples with X-rays to study how they scatter the light. The scientists’ work with lysozyme represents the first-ever high-resolution experiments employing serial femtosecond crystallography--the split-second imaging of tiny crystals using ultrashort, ultrabright X-ray laser pulses.

The technique utilized a higher resolution than earlier achieved using X-ray lasers, allowing scientists to use smaller crystals than typical with other methods, and could also enable researchers to view molecular dynamics in a way never before possible. “We were able to actually visualize the structure of the molecule at a resolution so high we start to infer the position of individual atoms,” said Dr. Sébastien Boutet, a staff scientist at LCLS who led the research. “Not only that, but the structure we observed matches the known structure of lysozyme and shows no significant sign of radiation damage, despite the fact that the pulses completely destroy the sample. This is the first high-resolution demonstration of the ‘diffraction-before-destruction’ technique on biological samples, where we’re able to measure a sample before the powerful pulses of the LCLS damage it.”

The scientists selected lysozyme as the first sample for their research because it is easy to crystallize and has been widely studied. Their research not only determined lysozyme’s structure at such high resolution that it showed individual amino acids, but also demonstrated the ability to utilize very small crystals for a range of applications. Dr. Boutet reported that the team has also studied more complex proteins and systems that they are analyzing now.

Ultimately, scientists using LCLS are driving toward an atomic- and molecular-scale understanding of complex biologic systems--such as the membrane proteins that are critical in cell functions and the processes that fuel photosynthesis--which could lead to findings in a range of sciences, from pharmaceutical advances to new sources of alternative energy.

The experiment was the first study performed on the new coherent X-ray imaging (CXI) instrument, a “molecular camera” designed, constructed, and commissioned by SLAC and now available to the scientific community. Also key to the study was a novel custom-made detector, the Cornell-SLAC pixel array detector (CSPAD), developed in collaboration between Cornell University (Ithaca, NY, USA) and SLAC for use at the CXI instrument. “This important demonstration shows that the technique works, and it paves the way for a lot of exciting experiments to come,” concluded Dr. Boutet.

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