3L2W

Crystal structure of the Prototype Foamy Virus (PFV) intasome in complex with manganese and GS9137 (Elvitegravir)

Summary for 3L2W

• Entry DOI: 10.2210/pdb3l2w/pdb
• Related: 3DLR 3L2Q 3L2R 3L2S 3L2T 3L2U 3L2V
• Descriptor: Integrase, 5'-D(*AP*TP*TP*GP*TP*CP*AP*TP*GP*GP*AP*AP*TP*TP*TP*TP*GP*TP*A)-3', 5'-D(*TP*AP*CP*AP*AP*AP*AP*TP*TP*CP*CP*AP*TP*GP*AP*CP*A)-3', ... (8 entities in total)
• Functional Keywords: protein-dna complex, tetramer, dna integration, endonuclease, metal-binding, multifunctional enzyme, nuclease, nucleotidyltransferase, nucleus, transferase, viral nucleoprotein, virion, zinc, dna-binding, zinc binding, hhcc motif, viral protein, recombination, recombination-dna complex, recombination/dna
• Biological source: Human spumaretrovirus (SFVcpz(hu))
• Cellular location: Integrase: Virion (Potential). Protease/Reverse transcriptase/ribonuclease H: Host nucleus (By similarity): P14350
• Total number of polymer chains: 4
• Total formula weight: 101006.13

Authors

Hare, S.,Gupta, S.S.,Cherepanov, P. (deposition date: 2009-12-15, release date: 2010-02-09, Last modification date: 2023-11-01)

Primary citation

Hare, S.,Gupta, S.S.,Valkov, E.,Engelman, A.,Cherepanov, P.
Retroviral intasome assembly and inhibition of DNA strand transfer
Nature, 464:232-236, 2010

PubMed Abstract: Integrase is an essential retroviral enzyme that binds both termini of linear viral DNA and inserts them into a host cell chromosome. The structure of full-length retroviral integrase, either separately or in complex with DNA, has been lacking. Furthermore, although clinically useful inhibitors of HIV integrase have been developed, their mechanism of action remains speculative. Here we present a crystal structure of full-length integrase from the prototype foamy virus in complex with its cognate DNA. The structure shows the organization of the retroviral intasome comprising an integrase tetramer tightly associated with a pair of viral DNA ends. All three canonical integrase structural domains are involved in extensive protein-DNA and protein-protein interactions. The binding of strand-transfer inhibitors displaces the reactive viral DNA end from the active site, disarming the viral nucleoprotein complex. Our findings define the structural basis of retroviral DNA integration, and will allow modelling of the HIV-1 intasome to aid in the development of antiretroviral drugs.

PubMed: 20118915
DOI: 10.1038/nature08784

Experimental method

X-RAY DIFFRACTION (3.2 Å)