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TitleB-to-A transition in target DNA during retroviral integration.
Journal, issue, pagesNucleic Acids Res, Vol. 50, Issue 15, Page 8898-8918, Year 2022
Publish dateAug 26, 2022
AuthorsIlona K Jóźwik / Wen Li / Da-Wei Zhang / Doris Wong / Julia Grawenhoff / Allison Ballandras-Colas / Sriram Aiyer / Peter Cherepanov / Alan N Engelman / Dmitry Lyumkis /
PubMed AbstractIntegration into host target DNA (tDNA), a hallmark of retroviral replication, is mediated by the intasome, a multimer of integrase (IN) assembled on viral DNA (vDNA) ends. To ascertain aspects of ...Integration into host target DNA (tDNA), a hallmark of retroviral replication, is mediated by the intasome, a multimer of integrase (IN) assembled on viral DNA (vDNA) ends. To ascertain aspects of tDNA recognition during integration, we have solved the 3.5 Å resolution cryo-EM structure of the mouse mammary tumor virus (MMTV) strand transfer complex (STC) intasome. The tDNA adopts an A-like conformation in the region encompassing the sites of vDNA joining, which exposes the sugar-phosphate backbone for IN-mediated strand transfer. Examination of existing retroviral STC structures revealed conservation of A-form tDNA in the analogous regions of these complexes. Furthermore, analyses of sequence preferences in genomic integration sites selectively targeted by six different retroviruses highlighted consistent propensity for A-philic sequences at the sites of vDNA joining. Our structure additionally revealed several novel MMTV IN-DNA interactions, as well as contacts seen in prior STC structures, including conserved Pro125 and Tyr149 residues interacting with tDNA. In infected cells, Pro125 substitutions impacted the global pattern of MMTV integration without significantly altering local base sequence preferences at vDNA insertion sites. Collectively, these data advance our understanding of retroviral intasome structure and function, as well as factors that influence patterns of vDNA integration in genomic DNA.
External linksNucleic Acids Res / PubMed:35947647 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 3.8 Å
Structure data

26737

7usf

EMDB-26737, PDB-7usf:
Mouse mammary tumor virus strand transfer complex intasome
Method: EM (single particle) / Resolution: 3.5 Å

26744

7ut1

EMDB-26744, PDB-7ut1:
Higher-order assembly of multiple MMTV strand transfer complex intasomes
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-CA:
Unknown entry

Source
  • mouse mammary tumor virus
KeywordsHYDROLASE/DNA / Integrase-DNA complex / hydrolase / VIRAL PROTEIN / HYDROLASE-DNA complex

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