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Structural basis of sequence-specific RNA recognition by the antiviral factor APOBEC3G

Author

Listed:
  • Hanjing Yang

    (Molecular and Computational Biology, Departments of Biological Sciences and Chemistry)

  • Kyumin Kim

    (Molecular and Computational Biology, Departments of Biological Sciences and Chemistry)

  • Shuxing Li

    (Molecular and Computational Biology, Departments of Biological Sciences and Chemistry
    University of Southern California)

  • Josue Pacheco

    (Molecular and Computational Biology, Departments of Biological Sciences and Chemistry)

  • Xiaojiang S. Chen

    (Molecular and Computational Biology, Departments of Biological Sciences and Chemistry
    University of Southern California
    Keck School of Medicine
    University of Southern California)

Abstract

An essential step in restricting HIV infectivity by the antiviral factor APOBEC3G is its incorporation into progeny virions via binding to HIV RNA. However, the mechanism of APOBEC3G capturing viral RNA is unknown. Here, we report crystal structures of a primate APOBEC3G bound to different types of RNAs, revealing that APOBEC3G specifically recognizes unpaired 5’-AA-3’ dinucleotides, and to a lesser extent, 5’-GA-3’ dinucleotides. APOBEC3G binds to the common 3’A in the AA/GA motifs using an aromatic/hydrophobic pocket in the non-catalytic domain. It binds to the 5’A or 5’G in the AA/GA motifs using an aromatic/hydrophobic groove conformed between the non-catalytic and catalytic domains. APOBEC3G RNA binding property is distinct from that of the HIV nucleocapsid protein recognizing unpaired guanosines. Our findings suggest that the sequence-specific RNA recognition is critical for APOBEC3G virion packaging and restricting HIV infectivity.

Suggested Citation

  • Hanjing Yang & Kyumin Kim & Shuxing Li & Josue Pacheco & Xiaojiang S. Chen, 2022. "Structural basis of sequence-specific RNA recognition by the antiviral factor APOBEC3G," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35201-9
    DOI: 10.1038/s41467-022-35201-9
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    References listed on IDEAS

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    1. Hanjing Yang & Fumiaki Ito & Aaron D. Wolfe & Shuxing Li & Nazanin Mohammadzadeh & Robin P. Love & Maocai Yan & Brett Zirkle & Amit Gaba & Linda Chelico & Xiaojiang S. Chen, 2020. "Understanding the structural basis of HIV-1 restriction by the full length double-domain APOBEC3G," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    2. 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.
    3. Jennifer A. Bohn & Keyur Thummar & Ashley York & Alice Raymond & W. Clay Brown & Paul D. Bieniasz & Theodora Hatziioannou & Janet L. Smith, 2017. "APOBEC3H structure reveals an unusual mechanism of interaction with duplex RNA," Nature Communications, Nature, vol. 8(1), pages 1-9, December.
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    5. Bastien Mangeat & Priscilla Turelli & Gersende Caron & Marc Friedli & Luc Perrin & Didier Trono, 2003. "Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts," Nature, Nature, vol. 424(6944), pages 99-103, July.
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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.

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