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

DOI: 10.1038/s41467-020-18874-y DOI Help

Authors: Michal S. Barski (Imperial College London) , Jordan J. Minnell (Imperial College London) , Zuzana Hodakova (The Francis Crick Institute (Midland Road)) , Valerie Pye (The Francis Crick Institute) , Andrea Nans (The Francis Crick Institute) , Peter Cherepanov (Imperial College London; The Francis Crick Institute) , Goedele N. Maertens (Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 11

State: Published (Approved)
Published: October 2020
Diamond Proposal Number(s): 17221 , 12579

Open Access Open Access

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.

Journal Keywords: DNA; Electron microscopy; Infection; Recombinases

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Documents:
s41467-020-18874-y.pdf