Picosecond x-ray crystallography of a protein has been demonstrated for the first time, by a multinational collaboration (Philip Anfinrud, NIH, PhilipA@intra.niddk.nih.gov), enabling atom-scale movies of an important biomolecule as it performs a speedy function. This accomplishment will be presented at the upcoming American Crystallographic Association meeting from July 26-31 in Cincinnati (see also Schotte et al., Science, 20 June 2003).

While crystallographers have previously obtained frozen snapshots of thousands of proteins, they have yet to capture the full range of motion in even a single protein. Previous x-ray movies of proteins have been on the nanosecond time scale, which is too slow for capturing the steps of many protein processes.

Recently, however, at the European Synchrotron and Radiation Facility (ESRF) in France, researchers made picosecond-scale movies of a mutant myoglobin molecule getting rid of a toxic carbon monoxide (CO) molecule. Myoglobin is the protein that stores oxygen in muscle tissue. The researchers chose to study a mutant version of the protein because the highly strained atomic structure in part of the protein causes it to get rid of a CO molecule much more quickly than does ordinary myoglobin.

To capture this process, they first sent a 1-ps pulse of laser light to the protein to eject the CO. Immediately afterward, they illuminated the protein with intense, 150-ps x-ray pulses from the ESRF synchrotron. Crucial to this process was the ability to isolate single x-ray pulses from the synchrotron. A CCD camera recorded the patterns from the successive x-ray pulses as they passed through the protein.

The resulting movie showed the CO migrating to various sites in the protein, with the myoglobin rearranging its shape to accommodate the expulsion of the CO. In addition to enabling researchers to study many important transitions in proteins, the picosecond time-scale of these movies is commensurate with the timescale of many molecular dynamics simulations, allowing for closer comparison between theory and experiment.