Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists prove X-ray laser can solve protein structures from scratch

25.11.2013
SLAC's linac coherent light source reaches key milestone in decoding biological structures that were out of reach

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: Max Planck Society

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.

SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the U.S. Department of Energy Office of Science. To learn more, please visit http://www.slac.stanford.edu.

SLAC's LCLS is the world's most powerful X-ray free-electron laser. A DOE national user facility, its highly focused beam shines a billion times brighter than previous X-ray sources to shed light on fundamental processes of chemistry, materials and energy science, technology and life itself. For more information, visit lcls.slac.stanford.edu.

DOE's Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit science.energy.gov.

Citation: T. Barends et al., Nature, 24 November 2013 (10.1038/nature12773)

Andy Freeberg | EurekAlert!
Further information:
http://www.slac.stanford.edu

More articles from Life Sciences:

nachricht For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)

nachricht New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Touch Displays WAY-AX and WAY-DX by WayCon

27.06.2017 | Power and Electrical Engineering

Drones that drive

27.06.2017 | Information Technology

Ultra-compact phase modulators based on graphene plasmons

27.06.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>