2023-08-10 11:00 ~ 2023-08-10 12:00
地點: 生化所209研討室
主講人: Matthias Wolf 博士
主講人背景: 日本沖繩科學技術大學院大學分子冷凍電子顯微術單位教授
演講主持人: 徐尚德研究員
演講摘要:
Great effort has been devoted to discovering the basis of A3G-Vif interaction, the key event of HIV’s counteraction mechanism to evade antiviral innate immune response. Here we show reconstitution of the A3G-Vif complex and subsequent A3G ubiquitination in vitro and report the cryo-EM structure of the A3G-Vif complex at 2.8 Å resolution using solubility-enhanced variants of A3G and Vif. We present an atomic model of the A3G-Vif interface, which assembles via known amino acid determinants. This assembly is not achieved by protein-protein interaction alone, but also involves RNA. The cryo-EM structure and in vitro ubiquitination assays identify an adenine/guanine base preference for the interaction and a unique Vif-ribose contact. This establishes the biological significance of an RNA ligand. Further assessment of interactions between A3G, Vif, and RNA ligands show that the A3G-Vif assembly and subsequent ubiquitination can be controlled by amino acid mutations at the interface or by polynucleotide modification, suggesting that a specific chemical moiety would be a promising pharmacophore to inhibit the A3G-Vif interaction.
Paper reference (now published in NComms): https://www.nature.com/articles/s41467-023-39796-5 -Dr. Matthias Wolf
洽詢人員: 劉小姐
洽詢電話: 27855696#2061
洽詢信箱: liukchun@gate.sinica.edu.tw
中央研究院 生物化學研究所
