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Structural insights into RNA bridging between HIV-1 Vif and antiviral factor APOBEC3G

Author

Listed:
  • Takahide Kouno

    (Okinawa Institute of Science and Technology Graduate University)

  • Satoshi Shibata

    (Okinawa Institute of Science and Technology Graduate University
    Tottori University)

  • Megumi Shigematsu

    (Thomas Jefferson University)

  • Jaekyung Hyun

    (Okinawa Institute of Science and Technology Graduate University
    Sungkyunkwan University)

  • Tae Gyun Kim

    (Okinawa Institute of Science and Technology Graduate University
    Gyeongbuk Institute for Bio Industry)

  • Hiroshi Matsuo

    (Frederick National Laboratory for Cancer Research)

  • Matthias Wolf

    (Okinawa Institute of Science and Technology Graduate University
    Academia Sinica)

Abstract

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.

Suggested Citation

  • Takahide Kouno & Satoshi Shibata & Megumi Shigematsu & Jaekyung Hyun & Tae Gyun Kim & Hiroshi Matsuo & Matthias Wolf, 2023. "Structural insights into RNA bridging between HIV-1 Vif and antiviral factor APOBEC3G," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39796-5
    DOI: 10.1038/s41467-023-39796-5
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    References listed on IDEAS

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    1. Ann M. Sheehy & Nathan C. Gaddis & Jonathan D. Choi & Michael H. Malim, 2002. "Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein," Nature, Nature, vol. 418(6898), pages 646-650, August.
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    Cited by:

    1. Hanjing Yang & Josue Pacheco & Kyumin Kim & Ayub Bokani & Fumiaki Ito & Diako Ebrahimi & Xiaojiang S. Chen, 2024. "Molecular mechanism for regulating APOBEC3G DNA editing function by the non-catalytic domain," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Fumiaki Ito & Ana L. Alvarez-Cabrera & Kyumin Kim & Z. Hong Zhou & Xiaojiang S. Chen, 2023. "Structural basis of HIV-1 Vif-mediated E3 ligase targeting of host APOBEC3H," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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