The Ebola virus matrix protein VP40 forms distinct structures linked to distinct functions in the virus life cycle. Dimeric VP40 is a structural protein associated with virus assembly, while octameric, ring-shaped VP40 is associated with transcriptional control. In this study, we show that suitable nucleic acid is sufficient to trigger a dynamic transformation of VP40 dimer into the octameric ring. Deep sequencing reveals a binding preference of the VP40 ring for the 3′ untranslated region of cellular mRNA and a guanine- and adenine-rich binding motif. Complementary analyses of the nucleic-acid-induced VP40 ring by native mass spectrometry, electron microscopy, and X-ray crystal structures at 1.8 and 1.4 Å resolution reveal the stoichiometry of RNA binding, as well as an interface involving a key guanine nucleotide. The host factor-induced structural transformation of protein structure in response to specific RNA triggers in the Ebola virus life cycle presents unique opportunities for therapeutic inhibition.

埃博拉病毒基质蛋白 VP40 形成与病毒生命周期中不同功能相关的不同结构。二聚体 VP40 是与病毒组装相关的结构蛋白，而八聚体、环状 VP40 与转录控制相关。在这项研究中，我们表明合适的核酸足以触发 VP40 二聚体动态转化为八聚体环。深度测序揭示了 VP40 环对细胞 mRNA 的 3' 非翻译区和富含鸟嘌呤和腺嘌呤的结合基序的结合偏好。通过天然质谱、电子显微镜和 X 射线晶体结构以 1.8 和 1.4 Å 分辨率对核酸诱导的 VP40 环进行互补分析，揭示了 RNA 结合的化学计量，以及涉及关键鸟嘌呤核苷酸的界面。