4E7K

PFV integrase Target Capture Complex (TCC-Mn), freeze-trapped prior to strand transfer, at 3.0 A resolution

Summary for 4E7K

• Entry DOI: 10.2210/pdb4e7k/pdb
• Related: 3DLR 3OS2 3OY9 3OYA
• Descriptor: Pro-Pol polyprotein, DNA (5'-D(*AP*TP*TP*GP*TP*CP*AP*TP*GP*GP*AP*AP*TP*TP*TP*CP*GP*CP*A)-3'), DNA (5'-D(*TP*GP*CP*GP*AP*AP*AP*TP*TP*CP*CP*AP*TP*GP*AP*CP*A)-3'), ... (9 entities in total)
• Functional Keywords: protein-dna complex, tetramer, hhcc motif, endonuclease, metal-binding, multifunctional enzyme, nuclease, nucleotidyltransferase, nucleus, transferase, virion, dna-binding, zinc-binding, viral protein, recombination, viral protein-dna complex, recombination-dna complex, recombination/dna
• Biological source: Human spumaretrovirus (SFVcpz(hu)); More
• Cellular location: Integrase: Virion (Potential). Protease/Reverse transcriptase/ribonuclease H: Host nucleus (By similarity): P14350
• Total number of polymer chains: 5
• Total formula weight: 109646.95

Authors

Maertens, G.N.,Cherepanov, P. (deposition date: 2012-03-17, release date: 2012-05-23, Last modification date: 2023-09-13)

Primary citation

Hare, S.,Maertens, G.N.,Cherepanov, P.
3'-Processing and strand transfer catalysed by retroviral integrase in crystallo.
Embo J., 31:3020-3028, 2012

PubMed Abstract: Retroviral integrase (IN) is responsible for two consecutive reactions, which lead to insertion of a viral DNA copy into a host cell chromosome. Initially, the enzyme removes di- or trinucleotides from viral DNA ends to expose 3'-hydroxyls attached to the invariant CA dinucleotides (3'-processing reaction). Second, it inserts the processed 3'-viral DNA ends into host chromosomal DNA (strand transfer). Herein, we report a crystal structure of prototype foamy virus IN bound to viral DNA prior to 3'-processing. Furthermore, taking advantage of its dependence on divalent metal ion cofactors, we were able to freeze trap the viral enzyme in its ground states containing all the components necessary for 3'-processing or strand transfer. Our results shed light on the mechanics of retroviral DNA integration and explain why HIV IN strand transfer inhibitors are ineffective against the 3'-processing step of integration. The ground state structures moreover highlight a striking substrate mimicry utilized by the inhibitors in their binding to the IN active site and suggest ways to improve upon this clinically relevant class of small molecules.

PubMed: 22580823
DOI: 10.1038/emboj.2012.118

Experimental method

X-RAY DIFFRACTION (3.02 Å)