10 Feb 2009 05:00 AM
Creation Of First Crystal Structure Of An Intermediate Particle In Virus Assembly
The structure, described February 8 in an advance online publication of the journal Nature, provides fresh insights into the elegant dance that viral proteins perform to create the infectious structure that causes all manner of misery and disease, say researchers. While the virus they studied, HK97, only infects bacteria, well-known viruses such as herpes and HIV are also known to assemble an "intermediary" structure before morphing into its final assault-proof, infectious form.
"The principles of this multi-stage protein coat assembly will likely be similar across all complex viruses," says the study's senior author, Scripps Research Professor John E. Johnson. "But this process has never been seen before at this resolution, and now we known that what we thought happens, doesn't."
That's important, Johnson says, because if scientists understand how a virus builds its protective coat, they may be able to medically target vulnerabilities in the first stage of that assembly. "We believe that without its final shell to protect it, an immature virus will be much more defenseless to antiviral agents," he says.
Knowing how viruses build these vessels to protect the naked viral DNA inside is also useful in the field of medical nanotechnology, he adds. "The immature coat has lots of holes in it through which we could load drugs, and then seal it in the mature form to produce a potent delivery system," Johnson says.
Johnson and his research team have long studied HK97, and had "solved" the structure of the virus's mature outer coat. It is made up of 72 protein rings - 12 pentagons and 60 hexagons - locked together like the chain mail suits worn by knights. This coating forms the head of the virus, which is extremely small - thousands of times narrower than a human hair.
The thin viral armor offers protection and stability as well as freedom of movement, Johnson says. "This is a container that works very well."
But the researchers say they spent five "painful" years trying to produce a crystal structure of the intermediate particle they knew was assembled first…
"The principles of this multi-stage protein coat assembly will likely be similar across all complex viruses," says the study's senior author, Scripps Research Professor John E. Johnson. "But this process has never been seen before at this resolution, and now we known that what we thought happens, doesn't."
That's important, Johnson says, because if scientists understand how a virus builds its protective coat, they may be able to medically target vulnerabilities in the first stage of that assembly. "We believe that without its final shell to protect it, an immature virus will be much more defenseless to antiviral agents," he says.
Knowing how viruses build these vessels to protect the naked viral DNA inside is also useful in the field of medical nanotechnology, he adds. "The immature coat has lots of holes in it through which we could load drugs, and then seal it in the mature form to produce a potent delivery system," Johnson says.
Johnson and his research team have long studied HK97, and had "solved" the structure of the virus's mature outer coat. It is made up of 72 protein rings - 12 pentagons and 60 hexagons - locked together like the chain mail suits worn by knights. This coating forms the head of the virus, which is extremely small - thousands of times narrower than a human hair.
The thin viral armor offers protection and stability as well as freedom of movement, Johnson says. "This is a container that works very well."
But the researchers say they spent five "painful" years trying to produce a crystal structure of the intermediate particle they knew was assembled first…
