Aqueous solution structure of a hybrid lentiviral Tat peptide and a model of its interaction with HIV-1 TAR RNA.
Aqueous solution structure of a hybrid lentiviral Tat peptide and a model of its interaction with HIV-1 TAR RNA.
复制标题
杂合慢病毒 Tat 肽的水溶液结构及其与 HIV-1 TAR RNA 相互作用的模型。
DOI：
10.1080/07391102.1996.10508877
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
James,TL
中科院分区：
文献类型：
--
作者：
Mujeeb,A;Parslow,TG;Yuan,YC;James,TL
人类免疫缺陷病毒1型（HIV-1）编码一种称为达特的反式激活调节蛋白，该蛋白是病毒基因组有效转录所必需的。达特通过与新生病毒转录物上的特定RNA茎环元件（称为TAR）结合而起作用。结合的特异性主要由达特的短的高碱性结构域中的残基决定。生物活性肽在水溶液中的结构，该生物活性肽由10个氨基酸的HIV-1达特基本结构域与另一种慢病毒达特的核心调节结构域的15个氨基酸区段连接组成，即，马传染性贫血病毒（EIAV）的抗原性。约束数据集包括通过一个完整的弛豫矩阵分析从二维核奥弗豪泽效应（2D NOE）谱确定的质子间距离界限。通过距离几何程序DIANA生成了与实验数据一致的30个结构。随后的约束分子力学计算被用来定义的构象空间所涵盖的肽。大部分的25-mer肽在水溶液中呈现具有富含赖氨酸和亮氨酸的HIV-1基本结构域为α-螺旋的结构，并且EIAV核心结构域通过转角与基本结构域分离，并且其特征也在于新生螺旋。达特肽/TAR复合物可以用位于TAR的大沟中的基本α-螺旋来建模，使得保持推定的特异性赋予精氨酸的重要相互作用，并且需要大沟的非常轻微的加宽。
Human immunodeficiency virus, type 1, (HIV-1) encodes a transactivating regulatory protein, called Tat, which is required for efficient transcription of the viral genome. Tat acts by binding to a specific RNA stem-loop element, called TAR, on nascent viral transcripts. The specificity of binding is principally determined by residues in a short, highly basic domain of Tat. The structure in aqueous solution of a biologically active peptide, comprised of the ten-amino acid HIV-1 Tat basic domain linked to a 15-amino acid segment of the core regulatory domain of another lentiviral Tat, i.e., that from equine infectious anemia virus (EIAV), has been determined. The restraint data set includes interproton distance bounds determined from two-dimensional nuclear Overhauser effect (2D NOE) spectra via a complete relaxation matrix analysis. Thirty structures consistent with the experimental data were generated via the distance geometry program DIANA. Subsequent restrained molecular mechanics calculations were used to define the conformational space subtended by the peptide. A large fraction of the 25-mer peptide assumes a structure in aqueous solution with the lysine- and arginine-rich HIV-1 basic domain being a-helical and the EIAV core domain being separated from the basic domain by a turn and characterized by a nascent helix as well. The Tat peptide/TAR complex could be modeled with the basic a-helix lying in the major groove of TAR such that important interactions of a putative specificity-endowing arginine are maintained and very slight widening of the major groove is entailed.