Retroviral integrase

Retrovirus integrase enables the integration of viral DNA into the host genome, a critical step in the retroviral replication cycle.

They belong to eukaryotic retrotransposase family. The integration is permanent and ensures that the viral genome is copied with every cell division

Enzymatic reaction: The reaction involves three steps:

• 3' end processing: After reverse transcription, integrase binds to the ends of the newly synthesized viral double-stranded DNA and cleaves two nucleotides from each 3' end, preparing it for integration.
• Strand transfer (integration): The enzyme-virus-genome complex binds to the host DNA and mediates the insertion of the viral DNA into the host chromosomal DNA, joining the viral 3' ends to the host DNA in a staggered cut.
• Post-integration Repair: Host cell enzymes repair the gaps to complete the integration.

Domain: All retroviral integrasess contain three structurally conserved domains connected by flexible linkers: an N-terminal Zn2+-binding domain, a core catalytic domain with the characteristic DDE triad motif to chelate two catalytic Mg2+ ions, and a C-terminal SH3-like domain

• Zinc-binding domain: PF02022
• Integrase core demain: PF00665
• DNA-binding domain: PF00552

Mechanism: Retroviral integrases belong to the DDE enzyme family, named after a conserved Asp-Asp-Glu catalytic triad. The reaction requires divalent metal ions (Mgor Mn) for activity and the enzyme works as a multimer (typically a tetramer).