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VIRUS ENCASED IN CHAIN MAIL Crystallography nails down unusual catenane-linked structure
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cientists have found definitive evidence that the casing of a bacteriainfecting virus has an ingenious and apparently unique chain-mail-like linked structure that makes it astoundingly tough, despite the fact that, relatively speaking, it's paper thin. More than just a biological novelty, the discovery may pique the interest of chemists who could use this natural model to help design materials. Postdoctoral researcher William R. Wikoff and professor John E. Johnson at Scripps Research Institute and their colleagues at the University of Pittsburgh, Stanford University, and the University of Uppsala, Sweden, report their crystallographic determination—at near atomic resolution—of the structure of the sac that houses viral DNA in the bacteriophage HK97 [Science, 289,2129 (2000)]. Viral casings, known as capsids, are composed of proteins that self-assemble into various geometric shapes during viral production. The proteins in the HK97 capsid amass into an icosahedron composed of hexamers and pentamers. But then, in a highly unusual step, the proteins reach out and grab each other, forming linkages known as catenanes. Linkers of this sort, which are of great interest to chemists, have been seen in molecules such as DNA and small organics—but never in whole proteins. The chain mail system appears to be unique to this family of viruses, Johnson says. Also, many previously characterized capsids are different assemblages of the same protein, but the proteins comprising the HK97 capsid is different from all other known proteins. The HK97 capsid is very large, about 660 A across, although it's only 18 A thick—a "molecular balloon" as the authors call it. By rights, it shouldn't even be stable enough to exist, but the chain mail linkages provide the necessary strength. "It illustrates the creative lengths biology can go to in order to solve problems," says Peter E. Prevelige Jr., micro-
biology professor at the University of Alabama, Birmingham. Hints of the HK97 capsid's structure surfaced a few years ago in the lab of two
of the current paper's coauthors: professor Roger W. Hendrix and researcher Robert L Duda at the Pittsburgh Bacteriophage Institute at the University of Pittsburgh. They found that, although denaturing reagents easily dissolve most viral capsids into a soup of their subunits, the HK97 capsid refused to disintegrate. The only way they could get it apart was to treat it with a protein-snipping enzyme, a phenomenon that strongly suggested the proteins were linked. Calling the new work "extremely interesting," Michael F. Summers, chemistry and biochemistry professor at the University of Maryland, Baltimore County, notes that some viral capsids may stabilize themselves by cross-linking their subunits with disulfide bonds. Those bonds are reduced to allow the viral genetic material to escape. But that doesn't have to happen with HK97's DNA—it is ejected through a taillike structure—which may explain why it was able to evolve the catenane links, which are isoamide bonds between an asparagine of one subunit and a lysine of another. T h e Scripps group has already teamed up with chemists who are using the virus's ingenuity as a springboard for designing artificially linked systems. "It's breathtaking when you look at what this virus has achieved," Johnson says. "It's just like medieval armor." Elizabeth Wilson
CWC Treaty Inspections Pose Few Problems Industry's fears that implementation of the Chemical Weapons Convention (CWC) would be costly in terms of money spent on facility inspections, loss of trade secrets, and adverse publicity have not materialized—at least not yet. On-site inspections of U.S. plants began in May. To date, 10 sites have been inspected by teams of international inspectors and an 11th site is to be inspected this week. The Commerce Department estimates that a total of 18 sites will be inspected this year and maybe another 36 next year.
The 10 inspections have been held at plants producing, processing, or consuming Schedule 1 or Schedule 2 chemicals. Schedule 1 chemicals are actual chemical warfare agents, which no commercial chemical company produces. Schedule 2 chemicals are precursors to chemical weapons, but they also have some commercial utility. "All industry inspections have been completed successfully, and while a few significant issues have arisen, there have been no findings of noncompliance," said SEPTEMBER 25, 2000 C&EN
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