7PEL

CryoEM structure of simian T-cell lymphotropic virus intasome in complex with PP2A regulatory subunit B56 gamma

Replaces:  6Z2Y

Summary for 7PEL

• Entry DOI: 10.2210/pdb7pel/pdb
• Related: 6QBT 6QBV 6QBW 6TJU 6TOQ
• EMDB information: 11052
• Descriptor: Pol protein, Isoform 3 of PC4 and SFRS1-interacting protein,Isoform Gamma-2 of Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform, DNA (5'-D(*AP*CP*TP*GP*TP*GP*TP*TP*TP*GP*GP*CP*GP*CP*TP*TP*CP*TP*CP*TP*C)-3'), ... (5 entities in total)
• Functional Keywords: integrase, transferase, deltaretrovirus, pp2a, b56, phosphatase, molecular mimicry, host factor, dna-binding, viral protein
• Biological source: Simian T-lymphotropic virus 1; More
• Total number of polymer chains: 10
• Total formula weight: 332223.95

Authors

Barski, M.,Pye, V.E.,Nans, A.,Cherepanov, P.,Maertens, G.N. (deposition date: 2021-08-10, release date: 2021-08-25, Last modification date: 2024-07-10)

Primary citation

Barski, M.S.,Minnell, J.J.,Hodakova, Z.,Pye, V.E.,Nans, A.,Cherepanov, P.,Maertens, G.N.
Cryo-EM structure of the deltaretroviral intasome in complex with the PP2A regulatory subunit B56gamma.
Nat Commun, 11:5043-, 2020

PubMed 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.

PubMed: 33028863
DOI: 10.1038/s41467-020-18874-y

Experimental method

ELECTRON MICROSCOPY (3.34 Å)