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Stanford Report, September 27, 2000

Odd shaped virus has coat of armor
Discovery by scientific team could have implications for nanotechnology

BY MARK SHWARTZ

Anyone suffering from a cold knows how tough and persistent viruses can be.

Now scientists have discovered that one type of virus actually comes equipped with an armored coat made of interlocking rings of protein.

The structure of this virus -- remarkably similar to chain mail suits worn by medieval knights -- had been predicted but never directly observed in a protein until now. Researchers say the discovery could have applications for the booming field of nanotechnology.

The armored virus was detected by an international team of scientists from Stanford, the Scripps Research Institute, the University of Pittsburgh and the University of Uppsala in Sweden. Their findings are published in the Sept. 22 issue of the journal Science.

A typical virus consists of little more than a chromosome of DNA or RNA wrapped in a protein coat.

Although viruses are among the simplest microbes, determining their molecular structure requires very sophisticated instrumentation.

The authors of the Science study used special micro-imaging techniques to analyze the outer coating of a virus called bacteriophage HK97.

Bacteriophages are viruses that only infect bacteria. They come in very bizarre shapes, some of which resemble NASA-designed satellites or Martian landers.

HK97 is no exception. It has an odd, balloon-shaped head attached to a short tail.

Analyzing this strange protein exterior required both electron microscopy and X-ray crystallography, says Hiro Tsuruta, a senior research associate with the Stanford Synchrotron Radiation Laboratory (SSRL) and the Department of Chemistry.

"The head of the virus is thousands of times narrower than a human hair," adds Tsuruta, a co-author of the Science study.

With the help of a small angle X-ray diffraction instrument at SSRL, Tsuruta and his colleagues were able to determine that HK97's head is made of 72 protein rings -- 12 pentagons and 60 hexagons -- locked together to form a protective coating that surrounds the virus's DNA.

"Its protein rings are cross-linked in a manner similar to the five-ring Olympic symbol," observes Tsuruta. "Together, the rings form a rigid, spherical cage shaped like a 20-sided soccer ball."

This unique chain-link structure makes the HK97 virus extraordinarily stable, adds Scripps biologist John E. Johnson, a co-author of the Science study, who also serves as a consulting professor at SSRL.

"The head is organized exactly like medieval armor," says Johnson, referring to the chain mail suits worn by knights in the Middle Ages. These protective outfits -- made of interwoven rings of iron -- were designed to deflect arrows while allowing maximum freedom of movement during battle.

The protein armor discovered in HK97 may have a similar function, allowing the virus mobility while protecting its precious cargo of DNA.

"The virus has developed a very clever way of keeping its DNA intact," notes Tsuruta.

Interlocking molecular rings, called catenanes, are an important focus of chemical research. Johnson points out that HK97's catenane structure should be of particular interest for nanotechnology, where engineers and scientists are designing new devices that will operate at the atomic scale.

"People are looking at viruses as containers," notes Johnson, "and the chain mail structure could provide a novel way to create a container that's very thin yet stable.

"No one expected that proteins could do this," adds Johnson, "and now we know they can."

Other contributors to the Science study are lead author William R. Wikoff of the Scripps Research Institute; Lars Liljas of the University of Uppsala; and Robert L. Duda and Roger W. Hendrix of the University of Pittsburgh.


X-ray crystallography reveals the head of an HK97 virus in fine detail. The head consists of 72 interconnected protein chains -- 16 pentagons and 60 hexagons. This kind of interlocking molecular structure had been predicted but never directly observed in a protein until now, and could have significant applications for nanotechnology. Courtesy: William Wikoff/Scripps Research Institute




This electron micrograph shows three HK97 bacteriophages. Each virus is thousands of times narrower than a human hair.
Courtesy: Robert Duda/University of Pittsburgh


A bacteriophage reproduces by injecting its DNA into a bacterium.
Image © James A. Sullivan, CELLS alive!