Frankel A D, Bredt D S, Pabo C O
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Science. 1988 Apr 1;240(4848):70-3. doi: 10.1126/science.2832944.
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.
来自HIV的反式激活蛋白Tat与金属离子形成金属连接的二聚体，金属离子桥接每个单体富含半胱氨酸的区域。这种新的排列方式不同于在其他真核调节蛋白中观察到的“锌指”结构域。紫外吸收光谱表明，每个单体的Tat结合两个Zn2+或两个Cd2+离子，Tat-金属复合物的电泳表明该蛋白形成金属连接的二聚体。部分蛋白酶解和圆二色光谱表明，金属结合主要在富含半胱氨酸的区域产生作用，对其他区域的折叠影响相对较小。这些结果为生物学研究提供了新方向，并为药物设计提供了新方法。
