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APOBEC3H structure reveals an unusual mechanism of interaction with duplex RNA

Author

Listed:
  • Jennifer A. Bohn

    (University of Michigan
    University of Michigan)

  • Keyur Thummar

    (The Rockefeller University
    The Rockefeller University)

  • Ashley York

    (The Rockefeller University
    The Rockefeller University)

  • Alice Raymond

    (The Rockefeller University
    The Rockefeller University)

  • W. Clay Brown

    (University of Michigan)

  • Paul D. Bieniasz

    (The Rockefeller University
    The Rockefeller University)

  • Theodora Hatziioannou

    (The Rockefeller University)

  • Janet L. Smith

    (University of Michigan
    University of Michigan)

Abstract

The APOBEC3 family of cytidine deaminases cause lethal hypermutation of retroviruses via deamination of newly reverse-transcribed viral DNA. Their ability to bind RNA is essential for virion infiltration and antiviral activity, yet the mechanisms of viral RNA recognition are unknown. By screening naturally occurring, polymorphic, non-human primate APOBEC3H variants for biological and crystallization properties, we obtained a 2.24-Å crystal structure of pig-tailed macaque APOBEC3H with bound RNA. Here, we report that APOBEC3H forms a dimer around a short RNA duplex and, despite the bound RNA, has potent cytidine deaminase activity. The structure reveals an unusual RNA-binding mode in which two APOBEC3H molecules at opposite ends of a seven-base-pair duplex interact extensively with both RNA strands, but form no protein–protein contacts. CLIP-seq analysis revealed that APOBEC3H preferentially binds to sequences in the viral genome predicted to contain duplexes, a property that may facilitate both virion incorporation and catalytic activity.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01309-6
    DOI: 10.1038/s41467-017-01309-6
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    Cited by:

    1. 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.
    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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