Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis

• 成果类型: Article
• 署名作者: Peng, Ruchao; Xu, Xin; Nepal, Binod; Gong, Yikang; Li, Fenglin; Ferretti, Max B.; Zhou, Mingyang; Lynch, Kristen W.; Burslem, George M.; Kortagere, Sandhya; Marmorstein, Ronen; Chang, Yi-Wei
• 署名单位: University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Drexel University; University of Pennsylvania
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12592
• DOI: 10.1126/science.adq7597
• 发表日期: 2025-05-15
• 关键词: a virus polymerase; cryo-em structure; nucleoprotein; protein; binding; Visualization; DYNAMICS; replication; mechanism; angstrom

摘要

Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex. By integrating cryo-electron microscopy single-particle analysis and cryo-electron tomography, we define the influenza RNP as a right-handed, antiparallel double helix with the viral RNA encapsidated in the minor groove. Individual nucleoprotein subunits are connected by a flexible tail loop that inserts into a conserved pocket in its neighbor. We visualize the viral polymerase in RNP at different functional states, revealing how it accesses the RNA template while maintaining the double-helical architecture of RNP by strand sliding. Targeting the tail loop binding interface, we identify lead compounds as potential anti-influenza inhibitors. These findings elucidate the molecular determinants underpinning influenza virus replication and highlight a promising target for antiviral development.