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STRUCTURAL STUDIES OF HIV-1 TAT PROTEIN

机译:HIV-1 TAT蛋白的结构研究

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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, Va14 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. [References: 26]
机译:Tat(反式激活蛋白)蛋白是调控慢病毒转录的早期RNA结合蛋白。这些蛋白质是所有已知慢病毒(例如人类免疫缺陷病毒(HIV)或马传染性贫血病毒(EIAV))生命周期中的必要组成部分。因此,Tat蛋白是干预慢病毒生长的药物的理想靶标。 HIV-1的共有RNA结合基序(TAR,反式激活反应元件)已得到很好的表征。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 Zaire 2分离株(HV1Z2)Tat蛋白的结构特征。通常,序列区域对应于蛋白质的结构域。它表现出16个氨基酸的疏水核心和17个氨基酸的谷氨酰胺丰富域。 NH2末端的一部分,Va14至Pro14,夹在这些结构域之间。两个高度灵活的结构域对应于一个富含半胱氨酸的区域和一个基本序列区域。在已知的Tat蛋白中,核心区域的16个氨基酸序列严格保守,并且HV1Z2 Tat蛋白的这些氨基酸的三维折叠与相应的EIAV Tat域的结构高度相似。 HV1Z2 Tat蛋白包含一个定义明确的COOH末端Arg-Gly-Asp(RGD)环,类似于最近确定的decorsin RGD环。 [参考:26]

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