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Science 1 April 1988:
Vol. 240. no. 4848, pp. 70 - 73
DOI: 10.1126/science.2832944
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Articles

Science, Vol 240, Issue 4848, 70-73
Copyright © 1988 by American Association for the Advancement of Science

articles

Tat protein from human immunodeficiency virus forms a metal-linked dimer

AD Frankel, DS Bredt, and CO Pabo

Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

Tat, the transactivating protein from HIV, forms a metal-linked dimer with metal ions bridging cysteine-rich regions from each monomer. This novel arrangement is distinct from the "zinc finger" domain observed in other eukaryotic regulatory proteins. Ultraviolet absorption spectra show that Tat binds two Zn2+ or two Cd2+ ions per monomer, and electrophoresis of the Tat-metal complexes demonstrates that the protein forms metal-linked dimers. Partial proteolysis and circular dichroism spectra suggest that metal binding has its primary effects in the cysteine-rich region and relatively little effect on the folding of other regions. These results suggest new directions for biological studies and new approaches to drug design.


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