In brilliant bursts of light from the world’s most powerful X-ray laser, physicists have taken snapshots of living viruses and see the 3-D shape of proteins frozen in nanometer-scale crystals.
The technique is described Feb. 3 in two Nature papers, and the images are the first biological subjects to be captured by bouncing X-rays off single particles.
“This really lets us see things that were invisible before,” said study co-author Marvin Seibert, a Stanford University physicist. “The most important thing is that scientists will be able to solve the structures of new biological molecules.”
To get a picture of a protein, researchers typically grow it in large crystals. For some proteins — especially those that span a cell’s membrane — this is difficult, even impossible. About 30,000 membrane proteins are found in the human body, but scientists know the shape of only six.
“Growing one of these crystals can be worth a Nobel,” Seibert said.
To make images with an X-ray laser, researchers sprayed viruses or individual proteins, frozen into crystals, into the path of an extremely powerful X-ray beam. According to the researchers, it was a billion times brighter than previous X-ray sources. The beam’s pulses lasted for quadrillionths of a second, scattering from the subject’s surface in the instant before it vaporized.
A camera recorded the scattering patterns, from which the subject’s shape could be reconstructed. From the combination of thousands of snapshots, three-dimensional images emerged. (To make the mandala-like image above, of a protein used in photosynthesis, the researchers took three million snapshots and combined the best 10,000.)
Now that researchers photograph single proteins, they have a shortcut to learning their shape, and thus to understanding how they work. Most drugs and diseases target these membrane proteins, so knowing their shape is important.
For the second study, researchers sprayed individual, unfrozen viruses into the X-ray beam, hoping to see their living shape. The subject was Mimivirus (see below), the largest known virus, so immense it’s infected by other viruses.
In other, more detailed, images the physicists could see a dark region they believe to be the genetic material. In an experiment ongoing now, using X-rays four times more powerful than those in the new study, the researchers are trying to capture the viral genome in 3-D.
If it works, they might be able to see how one virus differs from another, and how they develop over time.
“It’s very hot work,” said Seibert, “And it is happening literally right now.”
Images: 1) Three-dimensional rendering of the X-ray diffraction pattern for a mimivirus’ Photosystem I protein./Thomas White, DESY. 2) X-ray diffraction pattern of a single Mimivirus particle./Tomas Ekeberg, Uppsala University.
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Citations: “Femtosecond X-ray protein nanocrystallography.” By Henry Chapman, John Spence et al. Nature, Vol. 470, No. 7332, February 3, 2011.
“Single mimivirus particles intercepted and imaged with an X-ray laser.” By Marvin Seibert, Janos Hajdu et al. Nature, Vol. 470, No. 7332, February 3, 2011.