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.