SNAP output for PDB entry 7pel [SNAP web server]

PDB-id

7pel; SNAP-derived features in text and JSON formats; DNAproDB

Class

viral protein

Method

cryo-EM (3.34 Å)

Summary

Cryoem structure of simian t-cell lymphotropic virus intasome in complex with pp2a regulatory subunit b56 gamma

Reference

Barski MS, Minnell JJ, Hodakova Z, Pye VE, Nans A, Cherepanov P, Maertens GN (2020): "Cryo-EM structure of the deltaretroviral intasome in complex with the PP2A regulatory subunit B56gamma." Nat Commun, 11, 5043. doi: 10.1038/s41467-020-18874-y.

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.