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Structure of HIV-1 RRE stem-loop II identifies two conformational states of the high-affinity Rev binding site

Author

Listed:
  • Jerricho Tipo

    (The University of Texas Medical Branch
    Indiana University)

  • Keerthi Gottipati

    (Indiana University)

  • Michael Slaton

    (Indiana University)

  • Giovanni Gonzalez-Gutierrez

    (Indiana University)

  • Kyung H. Choi

    (The University of Texas Medical Branch
    Indiana University
    The University of Texas Medical Branch)

Abstract

During HIV infection, specific RNA-protein interaction between the Rev response element (RRE) and viral Rev protein is required for nuclear export of intron-containing viral mRNA transcripts. Rev initially binds the high-affinity site in stem-loop II, which promotes oligomerization of additional Rev proteins on RRE. Here, we present the crystal structure of RRE stem-loop II in distinct closed and open conformations. The high-affinity Rev-binding site is located within the three-way junction rather than the predicted stem IIB. The closed and open conformers differ in their non-canonical interactions within the three-way junction, and only the open conformation has the widened major groove conducive to initial Rev interaction. Rev binding assays show that RRE stem-loop II has high- and low-affinity binding sites, each of which binds a Rev dimer. We propose a binding model, wherein Rev-binding sites on RRE are sequentially created through structural rearrangements induced by Rev-RRE interactions.

Suggested Citation

  • Jerricho Tipo & Keerthi Gottipati & Michael Slaton & Giovanni Gonzalez-Gutierrez & Kyung H. Choi, 2024. "Structure of HIV-1 RRE stem-loop II identifies two conformational states of the high-affinity Rev binding site," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48162-y
    DOI: 10.1038/s41467-024-48162-y
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    References listed on IDEAS

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    1. Eva-Maria Schneeberger & Matthias Halper & Michael Palasser & Sarah Viola Heel & Jovana Vušurović & Raphael Plangger & Michael Juen & Christoph Kreutz & Kathrin Breuker, 2020. "Native mass spectrometry reveals the initial binding events of HIV-1 rev to RRE stem II RNA," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    2. Eunhye Lee & Paul J. Bujalowski & Tadahisa Teramoto & Keerthi Gottipati & Seth D. Scott & Radhakrishnan Padmanabhan & Kyung H. Choi, 2021. "Structures of flavivirus RNA promoters suggest two binding modes with NS5 polymerase," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    3. 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.
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