Attacking AIDS

Recently, James and his colleagues used their techniques to determine the structure of a protein segment that activates HIV to produce more virus. The protein is known as "Tat" for transactivating protein. Binding of Tat protein to RNA in the virus is believed to be a necessary step in recruiting cellular proteins that promote viral transcription -- the process by which the viral DNA is "transcribed" to create matching strands of RNA that, in turn, guide the process that produces the structural proteins and enzymes of a new virus.

James and his colleagues, with help from supercomputing at Pittsburgh, derived a structure for Tat protein. To the surprise of researchers, Tat's RNA-binding region forms an alpha-helical structure in solution. Because this region has many positively charged amino acids, says James, no one would have predicted this beforehand. "A driving force for this research is understanding the structural features that could make it possible to block Tat function and consequently impede viral replication. We're now using the Tat protein structure to try to find a molecule that will bind specifically with this structure."

The alpha-helical backbone segment (gold) of Tat protein. Two amino-acid sidechains (magenta and yellow) indicate the site at which the protein interacts with the transactivation response (TAR) sequence of RNA from HIV-1. This interaction plays a vital role in transcription of the HIV virus.

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