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HIV-1 Tat interactions with cellular 7SK and viral TAR RNAs identifies dual structural mimicry

Author

Listed:
  • Vincent V. Pham

    (Harvard University)

  • Carolina Salguero

    (Harvard University
    Universidad de los Andes)

  • Shamsun Nahar Khan

    (Harvard University
    East West University)

  • Jennifer L. Meagher

    (University of Michigan)

  • W. Clay Brown

    (University of Michigan)

  • Nicolas Humbert

    (Université de Strasbourg)

  • Hugues Rocquigny

    (Université de Strasbourg
    Inserm - U1259 MAVIVH. Morphogenèse et Antigénicité du VIH et des Virus des Hépatites)

  • Janet L. Smith

    (University of Michigan
    Department of Biological Chemistry, University of Michigan, Ann Arbor)

  • Victoria M. D’Souza

    (Harvard University)

Abstract

The HIV Tat protein competes with the 7SK:HEXIM interaction to hijack pTEFb from 7SK snRNP and recruit it to the TAR motif on stalled viral transcripts. Here we solve structures of 7SK stemloop-1 and TAR in complex with Tat’s RNA binding domain (RBD) to gain insights into this process. We find that 7SK is peppered with arginine sandwich motifs (ASM)—three classical and one with a pseudo configuration. Despite having similar RBDs, the presence of an additional arginine, R52, confers Tat the ability to remodel the pseudo configuration, required for HEXIM binding, into a classical sandwich, thus displacing HEXIM. Tat also uses R52 to remodel the TAR bulge into an ASM whose structure is identical to that of the remodeled ASM in 7SK. Together, our structures reveal a dual structural mimicry wherein viral Tat and TAR have co-opted structural motifs present in cellular HEXIM and 7SK for productive transcription of its genome.

Suggested Citation

  • Vincent V. Pham & Carolina Salguero & Shamsun Nahar Khan & Jennifer L. Meagher & W. Clay Brown & Nicolas Humbert & Hugues Rocquigny & Janet L. Smith & Victoria M. D’Souza, 2018. "HIV-1 Tat interactions with cellular 7SK and viral TAR RNAs identifies dual structural mimicry," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06591-6
    DOI: 10.1038/s41467-018-06591-6
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    Cited by:

    1. Ryan Damme & Kongpan Li & Minjie Zhang & Jianhui Bai & Wilson H. Lee & Joseph D. Yesselman & Zhipeng Lu & Willem A. Velema, 2022. "Chemical reversible crosslinking enables measurement of RNA 3D distances and alternative conformations in cells," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Shannon Ward & Alex Childs & Ceri Staley & Christopher Waugh & Julie A. Watts & Anna M. Kotowska & Rahul Bhosale & Aditi N. Borkar, 2024. "Integrating cryo-OrbiSIMS with computational modelling and metadynamics simulations enhances RNA structure prediction at atomic resolution," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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