Solution structure of the HIV-2 TAR-argininamide complex
Solution structure of the HIV-2 TAR-argininamide complex
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DOI：
10.1006/jmbi.1996.0879
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发表时间：
1997-04-04
影响因子：
5.6
通讯作者：
Williamson, JR
中科院分区：
文献类型：
--
作者：
Brodsky, AS;Williamson, JR
反式激活区 (TAR) RNA-Tat 蛋白相互作用对于人类免疫缺陷病毒 (HIV) 的转录激活非常重要。通过多维异核核磁共振研究了由两个碱基凸起 HIV-2 TAR 和精氨酸酰胺衍生物组成的这种相互作用的模型复合物。由于 HIV-2 TAR 复合物的光谱特性得到改善，与 HIV-1 TAR-精氨酰胺复合物的早期研究相比，在凸出区域观察到更多数量的 NOE。总共收集了 681 个 NOE 距离限制并用于确定 HIV-2 TAR-精氨酰胺复合物的溶液结构。正如该实验室之前提出的模型中所观察到的，两个 A 形茎同轴堆叠，关键的 U23 和精氨酰胺位于主凹槽中。包括非实验约束在内的模型计算表明，U23 与 A27 的氢键距离以内，与 U.A.U 碱基三元组的形成一致。碱基三联体的形成有助于打开主沟，以增加 G26 与来自精氨酰胺胍基的氢键供体的可及性。精氨酰胺结合通过在 A22 和 U23 碱基之间堆叠胍基团来稳定，形成精氨酰胺三明治。 (C) 1997 学术出版社有限公司。
The trans-activating region (TAR) RNA-Tat protein interaction is important for activation of transcription in the human immunodeficiency virus (HIV). A model complex for this interaction composed of the two base bulge HIV-2 TAR and the amide derivative of arginine was studied by multidimensional heteronuclear NMR. Because of the improved spectral properties of the HIV-2 TAR complex, a larger number of NOEs in the bulge region were observed than in earlier studies of the HIV-1 TAR-argininamide complex. A total of 681 NOE distance restraints were collected and used to determine the solution structure of the HIV-2 TAR-argininamide complex. As observed in the previously proposed model from this lab, the two A-form stems co-axially stack and the critical U23 and the argininamide are located in the major groove. Model calculations including non-experimental restraints indicate that U23 is within hydrogen bonding distance to A27 consistent with the formation of a U.A.U base-triple. Base-triple formation helps open the major groove to increase the accessibility of G26 to hydrogen bond donors from the guanidinium group of argininamide. Argininamide binding is stabilized by stacking of the guanidinium group between the bases of A22 and U23, forming an argininamide sandwich. (C) 1997 Academic Press Limited.