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Structure paper

TitleCryo-EM structure of the deltaretroviral intasome in complex with the PP2A regulatory subunit B56γ.
Journal, issue, pagesNat Commun, Vol. 11, Issue 1, Page 5043, Year 2020
Publish dateOct 7, 2020
AuthorsMichał S Barski / Jordan J Minnell / Zuzana Hodakova / Valerie E Pye / Andrea Nans / Peter Cherepanov / Goedele N Maertens /
PubMed AbstractHuman 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 ...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.
External linksNat Commun / PubMed:33028863 / PubMed Central
MethodsX-ray diffraction / EM (single particle)
Resolution1.8 - 3.34 Å
Structure data

PDB-6qbt:
Structure of the HTLV-2 integrase catalytic core domain in complex with magnesium (trimeric form)
Method: X-RAY DIFFRACTION / Resolution: 2.29 Å

PDB-6qbv:
Structure of the HTLV-2 integrase catalytic core domain in complex with magnesium (dimeric form)
Method: X-RAY DIFFRACTION / Resolution: 2.45 Å

PDB-6qbw:
Structure of the HTLV-2 integrase catalytic core domain in complex with calcium
Method: X-RAY DIFFRACTION / Resolution: 2.4 Å

PDB-6tju:
X-ray structure of C-terminal domain of human T-cell lymphotropic virus type 1 (HTLV-1)
Method: X-RAY DIFFRACTION / Resolution: 1.8 Å

PDB-6toq:
Crystal structure of a PP2A B56y/HTLV-1 integrase complex
Method: X-RAY DIFFRACTION / Resolution: 3.164 Å

PDB-7pel:
CryoEM structure of simian T-cell lymphotropic virus intasome in complex with PP2A regulatory subunit B56 gamma
Method: ELECTRON MICROSCOPY / Resolution: 3.34 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER

ChemComp-CA:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • human t-cell leukemia virus 2
  • human t-cell leukemia virus type i
  • homo sapiens (human)
  • simian t-lymphotropic virus 1
  • synthetic construct (others)
KeywordsTRANSFERASE / retrovirus / deltaretrovirus / integration / strand-transfer / nucleotidyltransferase / HTLV-1 / integrase / DNA-binding / SIGNALING PROTEIN / Phosphatase / complex / SLiM / dephosphorylation / cell signalling / motif mimicry / VIRAL PROTEIN / PP2A / B56 / molecular mimicry / host factor

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