Bayer P, Kraft M, Ejchart A, Westendorp M, Frank R, Rösch P
Lehrstuhl für Biopolymere und Bayreuther Institut für Makromolekülforschung Universität Bayreuth, Germany.
J Mol Biol. 1995 Apr 7;247(4):529-35. doi: 10.1006/jmbi.1995.0158.
Tat (trans-activator) proteins are early RNA binding proteins regulating lentiviral transcription. These proteins are necessary components in the life cycle of all known lentiviruses, such as the human immunodeficiency viruses (HIV) or the equine infectious anemia virus (EIAV). Tat proteins are thus ideal targets for drugs intervening with lentiviral growth. The consensus RNA binding motif (TAR, trans-activation responsive element) of HIV-1 is well characterized. Structural features of the 86 amino acid HIV-1, Zaire 2 isolate (HV1Z2) Tat protein in solution were determined by two dimensional (2D) nuclear magnetic resonance (NMR) methods and molecular dynamics (MD) calculations. In general, sequence regions corresponded to structural domains of the protein. It exhibited a hydrophobic core of 16 amino acids and a glutamine-rich domain of 17 amino acids. Part of the NH2 terminus, Val4 to Pro14, was sandwiched between these domains. Two highly flexible domains corresponded to a cysteine-rich and a basic sequence region. The 16 amino acid sequence of the core region is strictly conserved among the known Tat proteins, and the three-dimensional fold of these amino acids of HV1Z2 Tat protein was highly similar to the structure of the corresponding EIAV Tat domain. HV1Z2 Tat protein contained a well defined COOH-terminal Arg-Gly-Asp (RGD) loop similar to the recently determined decorsin RGD loop.
反式激活蛋白（Tat）是调节慢病毒转录的早期RNA结合蛋白。这些蛋白是所有已知慢病毒生命周期中的必要组成部分，如人类免疫缺陷病毒（HIV）或马传染性贫血病毒（EIAV）。因此，Tat蛋白是干预慢病毒生长的药物的理想靶点。HIV-1的共有RNA结合基序（反式激活应答元件，TAR）已得到充分表征。通过二维（2D）核磁共振（NMR）方法和分子动力学（MD）计算确定了溶液中86个氨基酸的HIV-1扎伊尔2型分离株（HV1Z2）Tat蛋白的结构特征。一般来说，序列区域与蛋白质的结构域相对应。它呈现出一个由16个氨基酸组成的疏水核心和一个由17个氨基酸组成的富含谷氨酰胺的结构域。NH2末端的一部分，从缬氨酸4到脯氨酸14，夹在这些结构域之间。两个高度灵活的结构域对应于富含半胱氨酸的区域和一个碱性序列区域。核心区域的16个氨基酸序列在已知的Tat蛋白中严格保守，并且HV1Z2 Tat蛋白的这些氨基酸的三维折叠与相应的EIAV Tat结构域的结构高度相似。HV1Z2 Tat蛋白包含一个定义明确的COOH末端精氨酸-甘氨酸-天冬氨酸（RGD）环，类似于最近确定的去皮质素RGD环。
