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 Synthetic nanoparticles achieve the complexity of protein molecules
24.01.2017 | Carnegie Mellon University

nachricht Immune Defense Without Collateral Damage
24.01.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Arctic melt ponds form when meltwater clogs ice pores

24.01.2017 | Earth Sciences

Synthetic nanoparticles achieve the complexity of protein molecules

24.01.2017 | Life Sciences

PPPL physicist uncovers clues to mechanism behind magnetic reconnection

24.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>