Berkeley Lab researchers develop first 3-D atomic-scale model of P22 virus that identifies the protein interactions crucial for its stability
Cryo-electron microscopy (cryo-EM)--which enables the visualization of viruses, proteins, and other biological structures at the molecular level--is a critical tool used to advance biochemical knowledge. Now Lawrence Berkeley National Laboratory (Berkeley Lab) researchers have extended cryo-EM's impact further by developing a new computational algorithm that was instrumental in constructing a 3-D atomic-scale model of bacteriophage P22 for the first time.
Over 20,000 two-dimensional cryo-EM images of bacteriophage P22 (also known as the P22 virus that infects the common bacterium Salmonella) from Baylor College of Medicine were used to make the model. The results were published by researchers from Baylor College of Medicine, Massachusetts Institute of Technology, Purdue University and Berkeley Lab in the Proceedings of the National Academies of Sciences earlier in March.
"This is a great example of how to exploit electron microscopy technology and combine it with new computational methods to determine a bacteriophage's structure," said Paul Adams, Berkeley Lab's Molecular Biophysics & Integrated Bioimaging division director and a co-author of the paper. "We developed the algorithms -- the computational code -- to optimize the atomic model so that it best fit the experimental data."
Pavel Afonine, a Berkeley Lab computational research scientist and paper co-author, took the lead in developing the algorithm using Phenix, a software suite used traditionally in X-ray crystallography for determining macromolecular structures.
The successful rendering of bacteriophage P22's 3-D atomic-scale model allows researchers to peek inside the virus' protein coats at resolution. It is the culmination of several years of work that previously had enabled Baylor College researchers to trace out most of the protein's backbone, but not the fine details, according to Corey Hryc, co-first author and a graduate student of Baylor biochemistry professor Wah Chiu.
"Thanks to this exquisite structural detail, we have determined the protein chemistry of the P22 virus," Chiu said. "I think it is important that we provide detailed annotations with the structure so other researchers can use it for their future experiments," he added. Chiu's lab has been using cryo-EM and computer reconstruction techniques to build 3-D molecular structures for almost 30 years.
And the findings could have valuable biological implications as well.
Thanks to the 3-D atomic-scale model, it's now "possible to see the interactions between the pieces making up the P22 virus, which are critical to making it stable," Adams said. This helps researchers figure out how to make chemicals that can bind to certain proteins. Adams underscores that the ability to understand the configuration of atoms in molecular space can be used to generate new insights into drug design and development.
The National Institutes of Health funded this work.
Lawrence Berkeley National Laboratory addresses the world's most urgent scientific challenges by advancing sustainable energy, protecting human health, creating new materials, and revealing the origin and fate of the universe. Founded in 1931, Berkeley Lab's scientific expertise has been recognized with 13 Nobel Prizes. The University of California manages Berkeley Lab for the U.S. Department of Energy's Office of Science. For more, visit http://www.
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.
Jon Weiner | EurekAlert!
New catalyst controls activation of a carbon-hydrogen bond
21.11.2017 | Emory Health Sciences
The main switch
21.11.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
21.11.2017 | Physics and Astronomy
21.11.2017 | Physics and Astronomy
21.11.2017 | Life Sciences