RNA Binding Sensitivity of Nonstructural Protein 8 Revealed by Small-Angle Neutron Scattering and Alphafold2 Prediction.

Jiang, Xin; Xu, Jinxin; Liao, Zhenyu; Wang, Na; Zuo, Taisen; Ma, Changli; Jiang, Hanqiu; Ke, Yubin et al. · ACS Nano · 2025

basic_science · Level V

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Abstract

The flexible structure enables nonstructural protein 8 (nsp8) to respond quickly to environmental changes, which are essential for RNA replication and transcription of SARS-CoV-2. In this work, small-angle neutron scattering and AlphaFold2 prediction were applied to characterize the structural change of SARS-CoV-2 nsp8 dimers and tetramers. The results demonstrated that the nsp8 tetramer with a more exposed core domain shows a low thermal stability. The exposed core domain increases its sensitivity to RNA and adapts its structure to interact with RNA. Our work reveals the structural difference between the two forms of SARS-CoV-2 nsp8s in the RNA synthesis process, which partly elucidates the molecular mechanism behind RNA replication of the RNA virus.

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