Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

ASU researchers develop new device to help image key proteins at room temperature

20.12.2013
A group of researchers from Arizona State University are part of a larger team reporting a major advance in the study of human proteins that could open up new avenues for more effective drugs of the future. The work is being reported in this week's Science magazine.

In the paper, "Serial femtosecond crystallography of G-protein-coupled receptors," the team reports that they have been successful in imaging at room temperature the structure of G protein-coupled receptors (GPCR) with the use of an x-ray free-electron laser.

GPCR's are a highly diverse group of membrane proteins that mediate cellular communication. Because of their involvement in key physiological and sensory processes in humans, they are thought to be prominent drug targets.

The method described in the paper was applied for the first time to this important class of proteins, for which the 2012 Nobel Prize was awarded to Brian Kobilka and Robert Lefkowitz, said John Spence, an Arizona State University professor of physics. Spence also is the director of science at National Science Foundation's BioXFEL Science and Technology Center and a team member on the Science paper.

"These GPCR's are the targets of a majority of drug molecules," Spence said, but they are notoriously difficult to work with. This is the first time structural observations of the GPCR's have been made at room temperature, allowing researchers to overcome several disadvantages of previous imaging methods of the proteins.

"Normally, protein crystallography is performed on frozen samples, to reduce the effects of radiation damage," Spence said. "But this new work was based on an entirely new approach to protein crystallography, called SFX (Serial Femtosecond Crystallography) developed jointly by ASU, the Deutsches Elektronen-Synchrotron (DESY) and the SLAC National Accelerator Laboratory."

"This method uses brief pulses of x-rays instead of freezing the sample to avoid damage, and so it reveals the structure which actually occurs in a cell at room temperature, not the frozen structure," Spence added. "The 50 femtosecond pulses (120 per second) 'outrun' radiation damage, giving a clear picture of the structure before it is vaporized by the beam."

The femtosecond crystallography technique could enable researchers to view molecular dynamics at a time-scale never observed before. Spence said the method basically operates by collecting the scattering for the image so quickly that images are obtained before the sample is destroyed by the x-ray beam.

By 'outrunning' radiation-damage processes in this way, the researchers can record the time-evolution of molecular processes at room temperature, he said.

Spence said ASU played a crucial role in the project described in Science, through the invention by Uwe Weierstall (an ASU physics professor) of an entirely new device for sample delivery suited to this class of proteins.

The lipic cubic phase (LCP) injector that Weierstall developed replaces the continuous stream of liquid (which sends a continuously refreshed stream of proteins across the pulsed x-ray beam) with a slowly moving viscous stream of 'lipid cubic phase solution,' which has the consistency of automobile grease.

"We call it our 'toothpaste jet,'" Spence said.

He added that the LCP solves three problems associated with previous SFX work, and made this new work possible:

•The viscosity slows the flow rate so the crystals emerge at about the same rate as the x-ray pulses come along, hence no protein is wasted. This is important for the study of human protein, which is more costly than diamond on a per gram basis.
•The "hit rate" is very high. Nearly all x-ray pulses hit protein particles.
•Most important, LCP is itself a growth medium for protein nanocrystals.
"A big problem with the SFX work we have been doing over the past four years is that people did not know how to make the required nanocrystals," Spence said. "Now it seems many can be grown in the LCP delivery medium itself."

The international team reporting the advance in Science includes researchers from the Scripps Research Institute, La Jolla, Calif., the Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany; the Department of Physics and the Department of Chemistry and Biochemistry at ASU, Tempe, Ariz.; SLAC National Accelerator Laboratory, Menlo Park, Calif.; Trinity College, Dublin, Ireland; Uppsala University, Sweden; University of Hamburg, Germany; and Center for Ultrafast Imaging, Hamburg, Germany.

Petra Fromme led the ASU group that helped plan the experiments, characterize the samples and assist with data collection. Other members of the ASU team include: Daniel James, Dingjie Wang, Garrett Nelson, Uwe Weierstall, Nadia Zatsepin, Richard Kirian, Raimund Fromme, Shibom Basu, Christopher Kupitz, Kimberley Rendek, Ingo Grotjohann, and John Spence.

Source:
John Spence, (480) 965-6486
Media contact:
Skip Derra, (480) 965-4823; skip.derra@asu.edu

Skip Derra | EurekAlert!
Further information:
http://www.asu.edu

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>