Featured Research

from universities, journals, and other organizations

X-ray laser can solve protein structures from scratch

Date:
November 24, 2013
Source:
DOE/SLAC National Accelerator Laboratory
Summary:
A study shows for the first time that X-ray lasers can be used to generate a complete 3-D model of a protein without any prior knowledge of its structure.

This 3-D rendering of a lysozyme molecule shows two gadolinium atoms bound to it. Researchers soaked lysozyme crystals in a solution containing the metal gadolinium to help improve imaging quality in an experiment at SLAC's Linac Coherent Light Source X-ray laser. The experiment proved that LCLS can resolve the lysozyme structure without using data obtained earlier, and researchers hope to use similar techniques to reconstruct important unsolved proteins.
Credit: Copyright Max Planck Society

A study shows for the first time that X-ray lasers can be used to generate a complete 3-D model of a protein without any prior knowledge of its structure.

An international team of researchers working at the Department of Energy's (DOE) SLAC National Accelerator Laboratory produced from scratch an accurate model of lysozyme, a well-studied enzyme found in egg whites, using the Linac Coherent Light Source (LCLS) X-ray laser and sophisticated computer analysis tools.

The experiment proves that X-ray lasers can play a leading role in studying important biomolecules of unknown structure. The special attributes of LCLS, which allow the study of very small crystals, could cement its role in hunting down many important biological structures that have so far remained out of reach because they form crystals too small for analysis with conventional X-ray sources.

"Determining protein structures using X-ray lasers requires averaging a gigantic amount of data to get a sufficiently accurate signal, and people wondered if this really could be done," said Thomas Barends, a staff scientist at the Max Planck Institute for Medical Research in Germany who participated in the research. "Now we have experimental evidence. This really opens the door to new discoveries."

Collaborators from SLAC and Arizona State University also participated in the research, which was published Nov. 24 in Nature.

The underlying technique, called X-ray crystallography, is credited with solving the vast majority of all known protein structures and is associated with numerous Nobel Prizes since its first use just over a century ago.

Protein structures tie directly to their functions, such as how they bind and interact with other molecules, and thus provide vital details for developing highly targeted disease-fighting drugs. But many protein structures that are considered promising targets for new medicines remain unknown, mainly because they don't form crystals that can be deciphered with existing techniques.

This work is the latest in a rapid progression of important advances at LCLS, which began operations for users in 2010. For example, last year researchers used LCLS to determine the structure of an enzyme that can hold African sleeping sickness in check, which makes it a promising drug target. However, those previous studies relied on data from similar, known structures to fill in common data gaps.

For this study the researchers chose lysozyme, whose structure has been known for decades, because it offered a good test of whether their method produced accurate results. They soaked lysozyme crystals in a solution containing gadolinium, a metal that bonded with the lysozyme to produce a strong signal when subjected to the intense X-ray light. It was this signal from the gadolinium atoms that enabled exact reconstruction of the lysozyme molecule.

The team hopes to adapt and refine the technique to explore more complex proteins such as membrane proteins, which serve a range of important cellular functions and are the target of more than half of all new drugs in development. Only a small fraction of the thousands of membrane proteins have been completely mapped.

"This study is an important milestone on which the field will build further," said John R. Helliwell, emeritus professor of chemistry at the University of Manchester and formerly a director of the Synchrotron Radiation Source at Daresbury Laboratory in England. "The X-ray laser is bringing new opportunities and new ideas for 3-D structure determination of ever-smaller samples. The use of computers to automate this process is a triumph."

Barends said the latest results are a remarkable achievement, given that it took just a few years for LCLS to reach this milestone. "Further improvements in X-ray detectors, software and crystal formation and delivery techniques should enable more discoveries in the coming years," he said.


Story Source:

The above story is based on materials provided by DOE/SLAC National Accelerator Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. Thomas R. M. Barends, Lutz Foucar, Sabine Botha, R. Bruce Doak, Robert L. Shoeman, Karol Nass, Jason E. Koglin, Garth J. Williams, Sιbastien Boutet, Marc Messerschmidt, Ilme Schlichting. De novo protein crystal structure determination from X-ray free-electron laser data. Nature, 2013; DOI: 10.1038/nature12773

Cite This Page:

DOE/SLAC National Accelerator Laboratory. "X-ray laser can solve protein structures from scratch." ScienceDaily. ScienceDaily, 24 November 2013. <www.sciencedaily.com/releases/2013/11/131124200506.htm>.
DOE/SLAC National Accelerator Laboratory. (2013, November 24). X-ray laser can solve protein structures from scratch. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2013/11/131124200506.htm
DOE/SLAC National Accelerator Laboratory. "X-ray laser can solve protein structures from scratch." ScienceDaily. www.sciencedaily.com/releases/2013/11/131124200506.htm (accessed October 21, 2014).

Share This



More Matter & Energy News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gulfstream G500, G600 Unveiling

Gulfstream G500, G600 Unveiling

Flying (Oct. 20, 2014) — Watch Gulfstream's public launch of the G500 and G600 at their headquarters in Savannah, Ga., along with a surprise unveiling of the G500, which taxied up under its own power. Video provided by Flying
Powered by NewsLook.com
Japanese Scientists Unveil Floating 3D Projection

Japanese Scientists Unveil Floating 3D Projection

Reuters - Innovations Video Online (Oct. 20, 2014) — Scientists in Tokyo have demonstrated what they say is the world's first 3D projection that floats in mid air. A laser that fires a pulse up to a thousand times a second superheats molecules in the air, creating a spark which can be guided to certain points in the air to shape what the human eye perceives as an image. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Hey, Doc! Sewage, Beer and Food Scraps Can Power Chevrolet’s Bi-Fuel Impala

Hey, Doc! Sewage, Beer and Food Scraps Can Power Chevrolet’s Bi-Fuel Impala

3BL Media (Oct. 20, 2014) — Hey, Doc! Sewage, Beer and Food Scraps Can Power Chevrolet’s Bi-fuel Impala Video provided by 3BL
Powered by NewsLook.com
What We Know About Microsoft's Rumored Smartwatch

What We Know About Microsoft's Rumored Smartwatch

Newsy (Oct. 20, 2014) — Microsoft will reportedly release a smartwatch that works across different mobile platforms, has a two-day battery life and tracks heart rate. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Space & Time

Matter & Energy

Computers & Math

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins