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Scientists, interns bring structural biology's 'magic bullet' technique to x-ray lasers

Date:
November 10, 2016
Source:
SLAC National Accelerator Laboratory
Summary:
To understand the three-dimensional shape of a protein, scientists often rely on information from similar molecules. But sometimes, the protein is so unique that it’s not possible to find a close relative, they say.
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Paul Mgbam, LCLS summer intern, prepares samples for the selenium phasing experiment.
Credit: SLAC National Accelerator Laboratory

To understand the three-dimensional shape of a protein, scientists often rely on information from similar molecules. But sometimes, the protein is so unique that it's not possible to find a close relative.

In these instances, there's an imaging tool available called "de novo phasing." Researchers tag the molecule with an element that gives a characteristic signal and allows them to deduce the fine details of the complex 3-D structure of the protein.

A recent study at the Department of Energy's SLAC National Accelerator Laboratory successfully used this technique at an X-ray free-electron laser for the first time with the element selenium as a marker. The scientists were able to swap selenium with the natural sulfur in biotin, which they then bound to the biomolecule streptavidin, a protein produced by bacteria.

"This selenium phasing technique is called 'the magic bullet of structural biology' because it's very powerful," says Mark Hunter, SLAC scientist. "It gives a very strong signal and it's often simple to incorporate selenium into a biological structure."

Using 330,000 images captured by the Linac Coherent Light Source (LCLS), a DOE Office of Science User Facility, the research team determined the structure of the molecule from the data alone. Nature Communications published the study on Nov. 4.

Although the structure of the biotin-streptavidin compound is known, this information was not used, and the experiment shows the technique can be applied to unknown structures.

Seven of the co-authors on the paper were students in the 2015 summer LCLS intern program, managed by Alan Fry, director of the LCLS Laser Science and Technology Division. The interns prepared samples, ran trials and helped collect data during the study.

The experiment required the X-ray laser to work at its highest energy to-date, 12.8 keV, to get the characteristic signal from the bound selenium. "We had every single accelerating part of LCLS running," says Chun Hong Yoon, lead data analyst for the project. "The accelerator physicists have found ways of really increasing the output, in terms of photon energy. If there had been any failures, we would not have been able to do the work."

Selenium phasing is commonly used at synchrotrons, another bright source of light for X-ray experiments. This experiment marks the first time scientists have been able to use selenium for de novo phasing at an X-ray free-electron laser. Previous experiments at SLAC have used heavy metal atoms or sulfur as a marker for phasing.

If a sample is radiation-sensitive, it can be difficult to do the experiment at a synchrotron, where X-ray pulses tend to be longer and samples may be damaged during the measurement. Now, scientists can take advantage of the short, bright pulses of LCLS to conduct phasing studies with selenium, while greatly reducing the risk of conventional radiation damage that can complicate the results.

In the future, the LCLS researchers would like to develop a way to solve structures with fewer images, shortening the time required to conduct these types of experiments.


Story Source:

Materials provided by SLAC National Accelerator Laboratory. Note: Content may be edited for style and length.


Journal Reference:

  1. Mark S. Hunter, Chun Hong Yoon, Hasan DeMirci, Raymond G. Sierra, E. Han Dao, Radman Ahmadi, Fulya Aksit, Andrew L. Aquila, Halilibrahim Ciftci, Serge Guillet, Matt J. Hayes, Thomas J. Lane, Meng Liang, Ulf Lundström, Jason E. Koglin, Paul Mgbam, Yashas Rao, Lindsey Zhang, Soichi Wakatsuki, James M. Holton, Sébastien Boutet. Selenium single-wavelength anomalous diffraction de novo phasing using an X-ray-free electron laser. Nature Communications, 2016; 7: 13388 DOI: 10.1038/ncomms13388

Cite This Page:

SLAC National Accelerator Laboratory. "Scientists, interns bring structural biology's 'magic bullet' technique to x-ray lasers." ScienceDaily. ScienceDaily, 10 November 2016. <www.sciencedaily.com/releases/2016/11/161110085014.htm>.
SLAC National Accelerator Laboratory. (2016, November 10). Scientists, interns bring structural biology's 'magic bullet' technique to x-ray lasers. ScienceDaily. Retrieved May 26, 2017 from www.sciencedaily.com/releases/2016/11/161110085014.htm
SLAC National Accelerator Laboratory. "Scientists, interns bring structural biology's 'magic bullet' technique to x-ray lasers." ScienceDaily. www.sciencedaily.com/releases/2016/11/161110085014.htm (accessed May 26, 2017).

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