Researchers 'see' native virus structure at near-atomic levels
By Ruth SoRelle, M.P.H.
Science and microscopy are pushing the envelope by enabling researchers to "see" molecules and structures such as parts of viruses as resolutions that are approaching the atomic level.
"When you say atomic, you really need to get it down to 1.5 Ångström, said Wah Chiu, Ph.D., professor of biochemistry and molecular biology at Baylor College of Medicine and director of the National Center for Macromolecular Imaging. "We have another factor of two to go to reach atomic level."
Cryo-electron microscope and hundreds of desktops
However, with the aid of a cryo-electron microscope and the computing power of hundreds of computers at Purdue University in Indiana, he and a group of colleagues succeeded in seeing the three-dimensional structure of an entire bacterial virus shell at 4.5 Ångström resolution. An Ångström is 100 millionth of a centimeter.
The virus shell for the virus in question – epsilon 15 – is essentially a container, composed of 840 protein molecules that surround the genome of the virus – its genetic blueprint. This virus, epsilon15, infects Salmonella bacterium and belongs to the family of viruses believed to be the most abundant form of life on earth.
Recent Nature article
In a report in a recent issue of Nature, research groups at Baylor College of Medicine, Purdue University and the Massachusetts Institute of Technology were able to describe this structure at a level of detail never possible before.
Their success in visualizing epsilon15 at near atomic resolution is attributable to the power of a cryo-electron microscope funded by the National Center for Research Resources, distributed computing resources consisting of banks of desktop computer supported by the National Science Foundation and a novel model-building algorithm, said Chiu, whose National Center for Macromolecular Medicine is funded by the National Institutes of Health.
Protein staple
This virus shell is the first infectious bacterial virus seen at such high resolution. Matthew Baker, Ph.D., a co-author in the paper and an instructor in the department of biochemistry and molecular biology at BCM, said that the most exciting and unexpected finding from this three-dimensional structure was the discovery of a small protein sitting on top of the virus at various strategic points appearing to act like a staple to keep it intact.
Chiu credited Baker with developing the sophisticated structure-mining software that allowed the team to build the model of the particle at the 4.5 Ångström level.
"It took 1 million CPU (central processing unit in a computer cluster) hours to solve this structure," said Chiu. The paper's first author, Wen Jiang, Ph.D., of Purdue, a former member of Chiu's NIH Center at BCM, oversaw this step of the research in collaboration with his university's National Science Foundation High Performance Computing Center that makes use of idle computing power of desktop computers throughout Purdue University.
This technology opens up a new way for scientists to visualize a biological nanomachine such as a virus particle without the need of forming a crystal. These advances allowed the scientists to trace the topology of the viral coat protein from one end to the other.
Native conformation
"That means we could now trace the three-dimensional topology of a protein in its native conformation," Chiu said.
Others who took part in the research include Joanita Jakana of BCM and Peter R. WeigeIe and Jonathan King of MIT. Funding for this work came from the National Institutes of Health and the National Science Foundation. The report can be found at www.nature.com.
