Determining biomolecule structures with protein nanocrystals

Compiled by BioPhotonics staff

Experiments on laser-excited samples, 3-D image reconstruction and other femtosecond diffractive imaging applications could get a boost from a protein beam projector – a tiny aerojet nozzle that fires a constant stream of protein nanocrystals to determine the structures of biomolecules based on diffraction.

A research team at Arizona State University (ASU) developed a protein beam projector to collect more than 3 million clear diffraction pattern “snapshots” just before the crystals exploded in the strong ultrashort femtosecond x-ray pulses. The findings appear in two studies in Nature, Feb. 2, 2011 (doi: 10.1038/nature09750 and doi: 10.1038/nature09748), and demonstrate the potential of the x-ray free-electron laser – the Linac Coherent Light Source, or LCLS – for new uses in biology and medicine.

A schematic of the principle of femtosecond nanocrystallography. The protein beam injector, left, ejects photosystem I nanocrystals into a fully hydrated stream of mother liquor. The stream of crystals interacts with the LCLS free-electron laser x-ray beam, where the crystals instantly explode. Each laser pulse is so short that diffraction can be detected from each nanocrystal before it is destroyed. Courtesy of Petra Fromme, ASU.

Biologists have long struggled to gather images at the molecular level, but the resolution has been limited by damage resulting from the radiation used. Now they are studying what happens when a pulse of imaging radiation is used that terminates before any damage occurs, yet contains sufficient photons to generate a useful scattering pattern. This method, which uses a hard x-ray laser, has provided a way to unravel protein structures for biologists to better understand the structure and function of cells. The findings have opened doors for solving protein structures and will have an impact on the medical field and on development of clean energy. In addition, new drugs for cancer and infectious diseases soon will be possible. Funding was provided by the National Science Foundation and the NIH.