Proteins Bond Together to Protect DNA

PITTSBURGH—Proteins that make up the hollow capsid of bacteriophage HK97 protect the virus' DNA from harm by quickly mobilizing to form links that securely bind the capsid proteins together as DNA is inserted. Researchers at the University of Pittsburgh and The Scripps Research Institute are examining this activity of HK97, a virus that infects bacteria. HK97 has properties similar to some animal viruses, including herpesviruses. The researchers' findings are reported in the June 4 issue of Molecular Cell.

Robert Duda and Roger Hendrix, members of the University's Pittsburgh Bacteriophage Institute and assistant professor and professor, respectively, in Pitt's Department of Biological Sciences, are studying how viruses are assembled with Lu Gan and John Johnson, graduate student and professor, respectively, at The Scripps Research Institute in La Jolla, Calif.

Previous research has shown that HK97—first isolated from pig dung by a rice geneticist in Hong Kong—has some unique properties. Typically, as bacteriophages mature, the DNA-containing capsid is strengthened by many weak contacts between capsid proteins or by extra proteins that act as glue. In HK97, however, the mature capsid is stable because the proteins form chemical bonds, or cross-links, with each other as the capsid expands. HK97 was the first bacteriophage discovered to form these stabilizing cross-links.

Researchers now know that HK97 begins to form cross-links early in the maturation process, at the same time that the capsid expands in size and DNA is pumped inside. It was previously thought that the cross-links were the last step in the process. This research may help elucidate how and why proteins change their shape, interact with other proteins, and assemble themselves.

"Once we understand in detail how viruses get assembled from their parts, we can start to think about how we might use that knowledge to sabotage the life cycles," said Duda.

Researchers also are interested in a packaging signal that directs a maturation enzyme, called a protease, to its site of action inside the capsid during its assembly. If researchers determine the mechanism of the packaging signal, Duda speculates, then it possibly could be used to entrap useful biomolecules into nanoscale protein spheres.

HK97 bacteriophage is similar to the bacteriophage lambda, one of the most well-studied bacteriophages. They both have the characteristic long tail with a balloon-like capsid, which stores the DNA that is injected into the host bacteria. The capsid serves to protect the DNA during transport from one host to another.

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6/2/04/tmw