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TitleRetroviral integration into nucleosomes through DNA looping and sliding along the histone octamer.
Journal, issue, pagesNat Commun, Vol. 10, Issue 1, Page 4189, Year 2019
Publish dateSep 13, 2019
AuthorsMarcus D Wilson / Ludovic Renault / Daniel P Maskell / Mohamed Ghoneim / Valerie E Pye / Andrea Nans / David S Rueda / Peter Cherepanov / Alessandro Costa /
PubMed AbstractRetroviral integrase can efficiently utilise nucleosomes for insertion of the reverse-transcribed viral DNA. In face of the structural constraints imposed by the nucleosomal structure, integrase ...Retroviral integrase can efficiently utilise nucleosomes for insertion of the reverse-transcribed viral DNA. In face of the structural constraints imposed by the nucleosomal structure, integrase gains access to the scissile phosphodiester bonds by lifting DNA off the histone octamer at the site of integration. To clarify the mechanism of DNA looping by integrase, we determined a 3.9 Å resolution structure of the prototype foamy virus intasome engaged with a nucleosome core particle. The structural data along with complementary single-molecule Förster resonance energy transfer measurements reveal twisting and sliding of the nucleosomal DNA arm proximal to the integration site. Sliding the nucleosomal DNA by approximately two base pairs along the histone octamer accommodates the necessary DNA lifting from the histone H2A-H2B subunits to allow engagement with the intasome. Thus, retroviral integration into nucleosomes involves the looping-and-sliding mechanism for nucleosomal DNA repositioning, bearing unexpected similarities to chromatin remodelers.
External linksNat Commun / PubMed:31519882 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 4.2 Å
Structure data

EMDB-4692, PDB-6r0c:
Human-D02 Nucleosome Core Particle with biotin-streptavidin label
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-4693:
Structure of a human nucleosome at 3.5 A resolution
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-4960, PDB-6rny:
PFV intasome - nucleosome strand transfer complex
Method: EM (single particle) / Resolution: 3.9 Å

Chemicals

ChemComp-MN:
Unknown entry

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
  • human spumaretrovirus
  • pyrobaculum filamentous virus 1
KeywordsDNA BINDING PROTEIN / chromatin / nucleosome / retrovirus

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