DIMERIZATION OF THE TAT PROTEIN FROM HUMAN IMMUNODEFICIENCY VIRUS - A CYSTEINE-RICH PEPTIDE MIMICS THE NORMAL METAL-LINKED DIMER INTERFACE
DIMERIZATION OF THE TAT PROTEIN FROM HUMAN IMMUNODEFICIENCY VIRUS - A CYSTEINE-RICH PEPTIDE MIMICS THE NORMAL METAL-LINKED DIMER INTERFACE
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DOI：
10.1073/pnas.85.17.6297
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发表时间：
1988-09-01
影响因子：
11.1
通讯作者：
PABO, CO
中科院分区：
文献类型：
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作者：
FRANKEL, AD;CHEN, L;PABO, CO
我们已经合成了一个18个氨基酸的肽，它包含了人类免疫缺陷病毒达特蛋白的富含半胱氨酸的区域。先前在体外用完整的达特蛋白进行的实验表明，这些半胱氨酸作为金属配体，导致达特形成金属连接的二聚体。紫外吸收光谱表明，合成的肽（tat 21 -38）结合到Cd 2+或两个Zn 2+离子每个肽单体，和一些变化的圆二色性光谱中看到的金属结合。肽-金属复合物对蛋白水解消化完全耐受，并且质谱证明该肽形成金属连接的二聚体。该肽还可以与完整的达特蛋白联合收割机形成金属连接的异二聚体。如果这些异源二聚体不能反式激活病毒转录，那么tat 21 -38可能是设计治疗获得性免疫缺陷综合症药物的先导化合物。
We have synthesized an 18-amino acid peptide that contains the cysteine-rich region of the tat protein from human immunodeficiency virus. Previous experiments in vitro with the intact tat protein have shown that these cysteines serve as metal ligands, causing tat to form metal-linked dimers. Ultraviolet absorption spectra show that the synthetic peptide (tat21-38) binds to Cd2+ or two Zn2+ ions per peptide monomer, and some changes in the circular dichroism spectra are seen as the metals bind. The peptide-metal complexes are completely resistant to proteolytic digestion, and mass spectrometry demonstrates that this peptide forms metal-linked dimers. The peptide can also combine with the intact tat protein to form metal-linked heterodimers. If these heterodimers are unable to trans-activate viral transcription, tat21-38 could be a lead compound for designing drugs to treat acquired immunodeficiency syndrome.