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Cryo-EM structure of the deltaretroviral intasome in complex with the PP2A regulatory subunit B56γ

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  • Michał S. Barski

    (Imperial College London, St Mary’s Hospital, Department of Infectious Disease, Section of Virology)

  • Jordan J. Minnell

    (Imperial College London, St Mary’s Hospital, Department of Infectious Disease, Section of Virology)

  • Zuzana Hodakova

    (Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute)

  • Valerie E. Pye

    (Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute)

  • Andrea Nans

    (Structural Biology Science Technology Platform, The Francis Crick Institute)

  • Peter Cherepanov

    (Imperial College London, St Mary’s Hospital, Department of Infectious Disease, Section of Virology
    Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute)

  • Goedele N. Maertens

    (Imperial College London, St Mary’s Hospital, Department of Infectious Disease, Section of Virology)

Abstract

Human T-cell lymphotropic virus type 1 (HTLV-1) is a deltaretrovirus and the most oncogenic pathogen. Many of the ~20 million HTLV-1 infected people will develop severe leukaemia or an ALS-like motor disease, unless a therapy becomes available. A key step in the establishment of infection is the integration of viral genetic material into the host genome, catalysed by the retroviral integrase (IN) enzyme. Here, we use X-ray crystallography and single-particle cryo-electron microscopy to determine the structure of the functional deltaretroviral IN assembled on viral DNA ends and bound to the B56γ subunit of its human host factor, protein phosphatase 2 A. The structure reveals a tetrameric IN assembly bound to two molecules of the phosphatase via a conserved short linear motif. Insight into the deltaretroviral intasome and its interaction with the host will be crucial for understanding the pattern of integration events in infected individuals and therefore bears important clinical implications.

Suggested Citation

  • Michał S. Barski & Jordan J. Minnell & Zuzana Hodakova & Valerie E. Pye & Andrea Nans & Peter Cherepanov & Goedele N. Maertens, 2020. "Cryo-EM structure of the deltaretroviral intasome in complex with the PP2A regulatory subunit B56γ," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18874-y
    DOI: 10.1038/s41467-020-18874-y
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    Cited by:

    1. Allison Ballandras-Colas & Vidya Chivukula & Dominika T. Gruszka & Zelin Shan & Parmit K. Singh & Valerie E. Pye & Rebecca K. McLean & Gregory J. Bedwell & Wen Li & Andrea Nans & Nicola J. Cook & Hind, 2022. "Multivalent interactions essential for lentiviral integrase function," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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