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首页> 外文期刊>Journal of Molecular Biology >Structural Determinants of HIV-1 Nucleocapsid Protein for cTAR DNA Binding and Destabilization, and Correlation with Inhibition of Self-primed DNA Synthesis.
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Structural Determinants of HIV-1 Nucleocapsid Protein for cTAR DNA Binding and Destabilization, and Correlation with Inhibition of Self-primed DNA Synthesis.

机译：HIV-1核衣壳蛋白与cTAR DNA结合和去稳定化的结构决定因素，以及与抑制自引发DNA合成的关系。

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摘要

The nucleocapsid protein (NC) of human immunodeficiency virus type 1 (HIV-1) is formed of two highly conserved CCHC zinc fingers flanked by small basic domains. NC is required for the two obligatory strand transfers in viral DNA synthesis through its nucleic acid chaperoning properties. The first DNA strand transfer relies on NC's ability to bind and destabilize the secondary structure of complementary transactivation response region (cTAR) DNA, to inhibit self-priming, and to promote the annealing of cTAR to TAR RNA. To further investigate NC chaperone properties, our aim was to identify by fluorescence spectroscopy and gel electrophoresis, the NC structural determinants for cTAR binding and destabilization, and for the inhibition of self-primed DNA synthesis on a model system using a series of NC mutants and HIV-1 reverse transcriptase. NC destabilization and self-priming inhibition properties were found to be supported by the two fingers in their proper context and the basic (29)RAPRKKG(35) linker. The strict requirement of the native proximal finger suggests that its hydrophobic platform (Val13, Phe16, Thr24 and Ala25) is crucial for binding, destabilization and inhibition of self-priming. In contrast, only partial folding of the distal finger is required, probably for presenting the Trp37 residue in an appropriate orientation. Also, Trp37 and the hydrophobic residues of the proximal finger appear to be essential for the propagation of the melting from the cTAR ends up to the middle of the stem. Finally, both N-terminal and C-terminal basic domains contribute to cTAR binding but not to its destabilization.
机译：1型人类免疫缺陷病毒（HIV-1）的核衣壳蛋白（NC）由两个高度保守的CCHC锌指形成，两侧有小的基本结构域。通过核酸的分子伴侣特性，NC是病毒DNA合成中两条强制链转移所必需的。第一次DNA链转移依赖于NC结合和破坏互补反式激活反应区（cTAR）DNA二级结构，抑制自引发以及促进cTAR退火至TAR RNA的能力。为了进一步研究NC分子伴侣的性质，我们的目的是通过荧光光谱和凝胶电泳来鉴定cTAR结合和去稳定化的NC结构决定因素，以及在使用一系列NC突变体的模型系统上抑制自引发DNA合成的机制。 HIV-1逆转录酶。发现NC不稳定和自启动抑制属性由两个手指在适当的上下文中和基本的（29）RAPRKKG（35）接头支持。对天然近端手指的严格要求表明，其疏水平台（Val13，Phe16，Thr24和Ala25）对于结合，不稳定和抑制自引发至关重要。相反，仅需要远端手指的部分折叠，可​​能是为了以适当的方向呈现Trp37残基。同样，Trp37和近端手指的疏水残基似乎对于从cTAR末端到茎中部的融化传播至关重要。最后，N-末端和C-末端的基本结构域都有助于cTAR结合，但不会导致其不稳定。

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