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Structure paper

TitleA supramolecular assembly mediates lentiviral DNA integration.
Journal, issue, pagesScience, Vol. 355, Issue 6320, Page 93-95, Year 2017
Publish dateJan 6, 2017
AuthorsAllison Ballandras-Colas / Daniel P Maskell / Erik Serrao / Julia Locke / Paolo Swuec / Stefán R Jónsson / Abhay Kotecha / Nicola J Cook / Valerie E Pye / Ian A Taylor / Valgerdur Andrésdóttir / Alan N Engelman / Alessandro Costa / Peter Cherepanov /
PubMed AbstractRetroviral integrase (IN) functions within the intasome nucleoprotein complex to catalyze insertion of viral DNA into cellular chromatin. Using cryo-electron microscopy, we now visualize the ...Retroviral integrase (IN) functions within the intasome nucleoprotein complex to catalyze insertion of viral DNA into cellular chromatin. Using cryo-electron microscopy, we now visualize the functional maedi-visna lentivirus intasome at 4.9 angstrom resolution. The intasome comprises a homo-hexadecamer of IN with a tetramer-of-tetramers architecture featuring eight structurally distinct types of IN protomers supporting two catalytically competent subunits. The conserved intasomal core, previously observed in simpler retroviral systems, is formed between two IN tetramers, with a pair of C-terminal domains from flanking tetramers completing the synaptic interface. Our results explain how HIV-1 IN, which self-associates into higher-order multimers, can form a functional intasome, reconcile the bulk of early HIV-1 IN biochemical and structural data, and provide a lentiviral platform for design of HIV-1 IN inhibitors.
External linksScience / PubMed:28059770 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.78 - 8.2 Å
Structure data

14860

7zpp

EMDB-14860, PDB-7zpp:
Cryo-EM structure of the MVV CSC intasome at 4.5A resolution
Method: EM (single particle) / Resolution: 4.5 Å

4139

5m0r

EMDB-4139, PDB-5m0r:
Cryo-EM reconstruction of the maedi-visna virus (MVV) strand transfer complex
Method: EM (single particle) / Resolution: 8.2 Å

PDB-5llj:
Maedi-Visna virus (MVV) integrase C-terminal domain (residues 220-276)
Method: X-RAY DIFFRACTION / Resolution: 1.78 Å

PDB-5t3a:
Maedi-Visna virus (MVV) integrase CCD-CTD (residues 60-275)
Method: X-RAY DIFFRACTION / Resolution: 2.501 Å

Chemicals

ChemComp-CL:
Unknown entry / Chloride

ChemComp-HOH:
WATER / Water

ChemComp-ACT:
ACETATE ION / Acetate

ChemComp-MES:
2-(N-MORPHOLINO)-ETHANESULFONIC ACID / pH buffer*YM / MES (buffer)

Source
  • visna/maedi virus ev1 kv1772
  • visna-maedi virus
  • visna lentivirus (strain 1514)
  • maedi visna virus (strain kv1772)
  • synthetic construct (others)
  • visna/maedi virus
KeywordsVIRAL PROTEIN / integrase / visna/maedi virus / c-terminal domain / HYDROLASE / retrovirus / lentivirus / DNA-binding / Zn-binding / RNAseH fold / Visna virus integrase / catalytic core domain / intasome / MVV / nucleoprotein complex

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