Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein structures revealed at record pace

23.07.2009
Scientists at the U.S. Department of Energy's (DOE) Lawrence Berkeley National Laboratory have developed a fast and efficient way to determine the structure of proteins, shortening a process that often takes years into a matter of days.

The high-throughput protein pipeline could allow scientists to expedite the development of biofuels, decipher how extremophiles thrive in conditions that kill most organisms, and better understand how proteins carry out life's vital functions.

The technique will help scientists keep pace with the growing flood of data stemming from genomic studies of organisms and environmental samples such as seawater and soil. Every new gene identified in these studies codes for a protein, and the structure of each protein must be characterized in order to determine what it does. Current structural characterization techniques are slow, however, meaning newly discovered proteins and their many complexes keep piling up, their function remaining a mystery.

"There's a bottleneck in structural genomics, and our system addresses that," says Greg Hura, a scientist in Berkeley Lab's Physical Biosciences Division. He developed the technique with John Tainer of Berkeley Lab's Life Sciences Division and the Scripps Research Institute in La Jolla, CA. Michael Adams and other scientists from the University of Georgia also contributed to the research.

Their work is published in the July 20 online edition of the journal Nature Methods.

The team developed the protein pipeline at the Advanced Light Source (ALS), a national user facility located at Berkeley Lab that generates intense light for scientific research. At a beamline called SIBYLS, they used a technique called small angle x-ray scattering (SAXS), which can image a protein in its natural state, such as in a solution, and at a spatial resolution of about 10 angstroms, which is small enough to determine a protein's three-dimensional shape. The brilliant light generated by the Advanced Light Source minimizes the amount of material required for each experiment, which makes the technique practical for almost any biomolecule.

To maximize speed, Hura installed a robot that automatically pipettes protein samples into position so they can be analyzed by x-ray scattering. And to analyze the resulting data, they used the supercomputing resources of the U.S. Department of Energy's National Energy Research Scientific Computing Center (NERSC), which is based at Berkeley Lab. The supercomputer's clusters can churn through data for 20 proteins per week, or more than 1000 macromolecules per year.

The result is a system that moves at breakneck speed compared to current techniques used to determine the shape and structure of proteins: x-ray crystallography and nuclear magnetic resonance. Recently, in the span of one month, the team used the system to resolve the structure of 40 proteins from Pyrococcus furiosus, a microscopic extremophile that can live at 100°C.

"This would have taken several years with x-ray crystallography," says Hura. "What used to take years, now can takes weeks."

Adds Tainer, "We can now obtain structural information in solution on most samples, rather than the 15 percent obtained by the best of the current Structural Genomics Initiative efforts employing nuclear magnetic resonance and crystallography. "

The Berkeley Lab team chose P. furiosus because it is an intriguing candidate for the production of clean energy and other applications. It has a pathway that produces hydrogen, which is a potential alternative fuel. And many industrial processes are highly acidic and very hot — conditions that P. furiosus loves.

"If we could learn which of the organism's proteins allow it to thrive in these conditions, then maybe we can apply them to energy production and other applications," says Hura.

Future synthetic biology efforts may involve taking a useful protein or a network of proteins from one microbe, and importing it into another microbe. In order to do this, scientists must learn how much of the network needs to be imported and still have it be able to do its job. This requires analyzing individual proteins in hundreds of different conditions.

"This is where our system will have a big impact. We can do this type of structural analysis in a matter of weeks, as opposed to years with crystallography," says Hura.

Of course, such speed doesn't come without tradeoffs. X-ray crystallography yields extremely high-resolution images, while small angle x-ray scattering yields a protein's shape at a much lower resolution of about 10 angstroms (one angstrom is one ten-millionth of a millimeter).

But the level of information offered by x-ray crystallography isn't always necessary. Sometimes, simply knowing if one protein is similar in shape to another is enough to learn its function. And SAXS makes up for what it lacks in precision by providing accurate information on the shape, assembly, and conformational changes of proteins in solution.

"We can have less information and still answer the questions that need to be answered," says Hura, adding that their technique will help usher in the next phase of genomics research. "The number of genes being identified is growing at a huge rate. We need to keep pace with this and learn about all the proteins encoded in these genes."

Adds Tainer, "This pipeline is an example of the stunning impact we can achieve by combining physics and engineering with structural biology, which is possible at government labs like Berkeley Lab."

The multidisciplinary work, which was conducted at Berkeley Lab's Advanced Light Source at beamline 12.3.1, also known as SIBYLS (Structurally Integrated BiologY for Life Sciences), relied on resources provided by three separate offices within the DOE Office of Science (SC). This work itself was supported in part by SC's Office of Biological and Environmental Research (BER). The ALS is supported by SC's Office of Basic Energy Sciences, while the beamline is supported in part by BER. NERSC is funded by SC's Office of Advanced Scientific Computing.

To aid communication of results, the team created a web-accessible database, www.Bioisis.net, which archives all experimental details associated with each analyzed sample.

"Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS)" by Greg Hura, Angeli Menon, Michal Hammel, Robert P. Rambo, Farris Poole, Susan Tsutakawa, Francis Jenney, Scott Classen, Kenneth Frankel, Robert Hopkins, Sung-jae Yang, Joseph Scott, Bret Dillard, Michael Adams, and John Tainer is published online July 20 in the journal Nature Methods.

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California for the DOE Office of Science. Visit our website at http://www.lbl.gov.

Dan Krotz | EurekAlert!
Further information:
http://www.lbl.gov

More articles from Life Sciences:

nachricht Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

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

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>