"Blas Cabrera" Institute for Physical Chemistry, Spanish National Research Council, Serrano 119, Madrid 28006, Spain.
Nucleic Acids Res. 2023 Oct 13;51(18):10041-10048. doi: 10.1093/nar/gkad714.
The SARS-CoV-2 Nsp8 protein is a critical component of the RNA replicase, as its N-terminal domain (NTD) anchors Nsp12, the RNA, and Nsp13. Whereas its C-terminal domain (CTD) structure is well resolved, there is an open debate regarding the conformation adopted by the NTD as it is predicted as disordered but found in a variety of complex-dependent conformations or missing from many other structures. Using NMR spectroscopy, we show that the SARS CoV-2 Nsp8 NTD features both well folded secondary structure and disordered segments. Our results suggest that while part of this domain corresponding to two long α-helices forms autonomously, the folding of other segments would require interaction with other replicase components. When isolated, the α-helix population progressively declines towards the C-termini but surprisingly binds dsRNA while preserving structural disorder.
新型冠状病毒 2 号 Nsp8 蛋白是 RNA 复制酶的关键组成部分，因为其 N 端结构域（NTD）锚定 Nsp12、RNA 和 Nsp13。虽然它的 C 端结构域（CTD）结构已经得到很好的解析，但关于 NTD 所采用的构象存在争议，因为它被预测为无序，但在各种复杂的依赖构象中被发现，或者在许多其他结构中缺失。使用 NMR 光谱，我们表明新型冠状病毒 2 号 Nsp8 NTD 具有良好折叠的二级结构和无序片段。我们的结果表明，虽然该结构域的一部分对应两个长 α-螺旋可以自主形成，但其他片段的折叠将需要与其他复制酶组件相互作用。当被分离时，α-螺旋的数量逐渐向 C 端减少，但令人惊讶的是，它在保持结构无序的同时结合 dsRNA。
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