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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