3OY9

Crystal structure of the Prototype Foamy Virus (PFV) intasome in complex with manganese at 2.55 resolution

Replaces:  3L2S

Summary for 3OY9

• Entry DOI: 10.2210/pdb3oy9/pdb
• Related: 3DLR 3L2Q 3L2R 3L2U 3L2V 3L2W 3OYA 3OYB 3OYC 3OYD 3OYE 3OYF 3OYG 3OYH 3OYI 3OYJ 3OYK 3OYL 3OYM 3OYN
• Descriptor: PFV integrase, 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, dna integration, endonuclease, metal-binding, multifunctional enzyme, nuclease, nucleotidyltransferase, nucleus, transferase, viral nucleoprotein, virion, dna-binding, zinc binding, hhcc motif, viral protein, recombination, dna-binding protein-dna complex, viral protein-dna complex, viral protein/dna
• Biological source: Human spumaretrovirus (SFVcpz(hu)); More
• Cellular location: Integrase: Virion . Protease/Reverse transcriptase/ribonuclease H: Host nucleus : P14350
• Total number of polymer chains: 4
• Total formula weight: 100752.35

Authors

Hare, S.,Cherepanov, P. (deposition date: 2010-09-23, release date: 2010-10-20, Last modification date: 2023-09-06)

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 (2.55 Å)