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This article is from the In-Depth Report Advances against AIDS

Cracking Open AIDS's Shell

This striking ribbon diagram may hold a key to foiling the virus that causes AIDS. For the first time, scientists have been able to peer deep inside the human immunodeficiency virus (HIV-1) and describe the structure of a fragment from an egglike shell, or capsid, that envelops the genetic material within the virus. Such information is likely to help researchers locate chinks in the armor of HIV-1.

The image was created by Michael F. Summers, Rossitza K. Gitti, Brian M. Lee and Jill Walker, investigators with the Howard Hughes Medical Institute at the University of Maryland Baltimore County, along with a Wesley I. Sundquist and Shanghee Yoo from the University of Utah. In a report in the July 12 issue of Science, the researchers display a detailed picture of the central region of the HIV-1 capsid (CA) protein¿the molecule that makes up the shell containing the RNA and enzymes necessary for HIV-1 to replicate and infect its host. Computer-analyzed magnetic resonance imaging was used to decipher the molecule's complicated structure.

Summers and his collaborators, who have been pursuing the structure of the CA protein for six years, were stunned when they looked at their results. The protein is almost entirely composed of alpha helices¿the dominant corkscrew pattern seen here, in which the amino acids that make up the protein wind into a hollow cylinder shape. The alpha helices are disrupted by two abrupt "beta hairpin turns," or U-turns, as well as by a looplike formation. Such a structure has never before been seen among the proteins that make up the shields surrounding the genetic material in viruses.

The detailed new map of the CA protein will be of great interest to drug developers. Nestled within the protein is the binding site of cyclophilin A, an enzyme found in blood cells. HIV-1 snatches cyclophilin A from the cells it invades and incorporates the molecule into its own structure. Jeremy Luban and his colleagues at Columbia University have shown that if cyclophilin A is not present and bound by CA, then HIV-1 cannot replicate. Hence, if there is a way to block cyclophilin A from binding with the CA protein, it could be possible to neutralize the AIDS virus.
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