title: Tat protein from human immunodeficiency virus forms a metal-linked dimer.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: A D
authors.initials: AD
authors.lastname: Frankel
authors.forename: D S
authors.initials: DS
authors.lastname: Bredt
authors.forename: C O
authors.initials: CO
authors.lastname: Pabo
mesh_terms: D002104:Cadmium / Q000378:metabolism*; D002942:Circular Dichroism; D003035:Cobalt / Q000378:metabolism; D003545:Cysteine; D004591:Electrophoresis, Polyacrylamide Gel; D015696:Gene Products, tat; D006678:HIV / Q000032:analysis*; D046911:Macromolecular Substances; D008670:Metals / Q000378:metabolism; D009856:Oncogene Proteins, Viral; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011487:Protein Conformation; D013053:Spectrophotometry; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015696:Gene Products, tat; D046911:Macromolecular Substances; D008670:Metals; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments; D013438:Sulfhydryl Compounds; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D002104:Cadmium; D003035:Cobalt; D010447:Peptide Hydrolases; D015032:Zinc; D003545:Cysteine