Native mass spectrometry reveals the initial binding events of HIV-1 rev to RRE stem II RNA.
Native mass spectrometry reveals the initial binding events of HIV-1 rev to RRE stem II RNA.
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DOI：
10.1038/s41467-020-19144-7
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发表时间：
2020-11-13
影响因子：
16.6
通讯作者：
Breuker K
中科院分区：
文献类型：
--
作者：
Schneeberger EM;Halper M;Palasser M;Heel SV;Vušurović J;Plangger R;Juen M;Kreutz C;Breuker K
由rev反应元件（RRE）核糖核酸（RNA）和rev蛋白多分子组成的核输出复合物是开发人类免疫缺陷病毒1型（HIV-1）治疗策略的有希望的靶点，但它们的组装仍然知之甚少。使用天然质谱法，我们在这里发现rev最初结合到RRE IIB的上茎，从那里它被传递到允许rev二聚化的结合位点。新发现的结合区表明，不属于RRE stem IIB RNA内环的核苷酸对rev进行初始识别，这是先前确定的首选结合区。我们的研究突出了天然质谱法的独特能力，可以单独研究不同化学计量的RNA/蛋白质复合物的结合界面，并提供了对RRE/rev关联机制的详细了解，这对合理设计抗HIV-1感染的潜在药物具有重要意义。HIV-1 RNA结合蛋白rev促进病毒RNA的核输出。在这里，作者使用天然质谱法研究了rev衍生肽与HIV-1 RNA的rev应答元件之间的相互作用，为rev识别和募集提供了机制见解。
Nuclear export complexes composed of rev response element (RRE) ribonucleic acid (RNA) and multiple molecules of rev protein are promising targets for the development of therapeutic strategies against human immunodeficiency virus type 1 (HIV-1), but their assembly remains poorly understood. Using native mass spectrometry, we show here that rev initially binds to the upper stem of RRE IIB, from where it is relayed to binding sites that allow for rev dimerization. The newly discovered binding region implies initial rev recognition by nucleotides that are not part of the internal loop of RRE stem IIB RNA, which was previously identified as the preferred binding region. Our study highlights the unique capability of native mass spectrometry to separately study the binding interfaces of RNA/protein complexes of different stoichiometry, and provides a detailed understanding of the mechanism of RRE/rev association with implications for the rational design of potential drugs against HIV-1 infection. The HIV-1 RNA-binding protein rev facilitates nuclear export of viral RNA. Here, the authors use native mass spectrometry to study the interactions between rev-derived peptides and rev response elements of HIV-1 RNA, providing mechanistic insights into rev recognition and recruitment.
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