IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35201-9.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35201-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-35201-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. Joseph M. Watts & Kristen K. Dang & Robert J. Gorelick & Christopher W. Leonard & Julian W. Bess Jr & Ronald Swanstrom & Christina L. Burch & Kevin M. Weeks, 2009. "Architecture and secondary structure of an entire HIV-1 RNA genome," Nature, Nature, vol. 460(7256), pages 711-716, August.
    3. Hui Zhang & Bin Yang & Roger J. Pomerantz & Chune Zhang & Shyamala C. Arunachalam & Ling Gao, 2003. "The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA," Nature, Nature, vol. 424(6944), pages 94-98, July.
    4. 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.
    5. Xiao Xiao & Shu-Xing Li & Hanjing Yang & Xiaojiang S. Chen, 2016. "Crystal structures of APOBEC3G N-domain alone and its complex with DNA," Nature Communications, Nature, vol. 7(1), pages 1-11, November.
    6. 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.
    7. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Iraj Hosseini & Feilim Mac Gabhann, 2012. "Multi-Scale Modeling of HIV Infection in vitro and APOBEC3G-Based Anti-Retroviral Therapy," PLOS Computational Biology, Public Library of Science, vol. 8(2), pages 1-17, February.
    2. Vanessa B Soros & Wes Yonemoto & Warner C Greene, 2007. "Newly Synthesized APOBEC3G Is Incorporated into HIV Virions, Inhibited by HIV RNA, and Subsequently Activated by RNase H," PLOS Pathogens, Public Library of Science, vol. 3(2), pages 1-16, February.
    3. 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.
    4. Patric Jern & Rebecca A Russell & Vinay K Pathak & John M Coffin, 2009. "Likely Role of APOBEC3G-Mediated G-to-A Mutations in HIV-1 Evolution and Drug Resistance," PLOS Pathogens, Public Library of Science, vol. 5(4), pages 1-9, April.
    5. Hannah O. Ajoge & Tyler M. Renner & Kasandra Bélanger & Matthew Greig & Samar Dankar & Hinissan P. Kohio & Macon D. Coleman & Emmanuel Ndashimye & Eric J. Arts & Marc-André Langlois & Stephen D. Barr, 2023. "Antiretroviral APOBEC3 cytidine deaminases alter HIV-1 provirus integration site profiles," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Beth K Thielen & Kevin C Klein & Lorne W Walker & Mary Rieck & Jane H Buckner & Garrett W Tomblingson & Jaisri R Lingappa, 2007. "T Cells Contain an RNase-Insensitive Inhibitor of APOBEC3G Deaminase Activity," PLOS Pathogens, Public Library of Science, vol. 3(9), pages 1-15, September.
    7. Diako Ebrahimi & Hamid Alinejad-Rokny & Miles P Davenport, 2014. "Insights into the Motif Preference of APOBEC3 Enzymes," PLOS ONE, Public Library of Science, vol. 9(1), pages 1-9, January.
    8. Stefan Harjes & Harikrishnan M. Kurup & Amanda E. Rieffer & Maitsetseg Bayarjargal & Jana Filitcheva & Yongdong Su & Tracy K. Hale & Vyacheslav V. Filichev & Elena Harjes & Reuben S. Harris & Geoffrey, 2023. "Structure-guided inhibition of the cancer DNA-mutating enzyme APOBEC3A," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    9. 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.
    10. Jing Ma & Xiaoyu Li & Jian Xu & Quan Zhang & Zhenlong Liu & Pingping Jia & Jinming Zhou & Fei Guo & Xuefu You & Liyan Yu & Lixun Zhao & Jiandong Jiang & Shan Cen, 2013. "The Roles of APOBEC3G Complexes in the Incorporation of APOBEC3G into HIV-1," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-9, October.
    11. Atanu Maiti & Adam K. Hedger & Wazo Myint & Vanivilasini Balachandran & Jonathan K. Watts & Celia A. Schiffer & Hiroshi Matsuo, 2022. "Structure of the catalytically active APOBEC3G bound to a DNA oligonucleotide inhibitor reveals tetrahedral geometry of the transition state," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    12. Julia Köppke & Luise-Elektra Keller & Michelle Stuck & Nicolas D. Arnow & Norbert Bannert & Joerg Doellinger & Oya Cingöz, 2024. "Direct translation of incoming retroviral genomes," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    13. Joseph Hiatt & Judd F. Hultquist & Michael J. McGregor & Mehdi Bouhaddou & Ryan T. Leenay & Lacy M. Simons & Janet M. Young & Paige Haas & Theodore L. Roth & Victoria Tobin & Jason A. Wojcechowskyj & , 2022. "A functional map of HIV-host interactions in primary human T cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35201-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.