3HPG

Visna virus integrase (residues 1-219) in complex with LEDGF IBD: examples of open integrase dimer-dimer interfaces

Summary for 3HPG

• Entry DOI: 10.2210/pdb3hpg/pdb
• Related: 1K6Y 2B4J 3F9K 3HPH
• Descriptor: Integrase, PC4 and SFRS1-interacting protein, ZINC ION (3 entities in total)
• Functional Keywords: protein-protein complex, tetramer, dna integration, endonuclease, magnesium, metal-binding, multifunctional enzyme, nuclease, nucleotidyltransferase, nucleus, transferase, viral nucleoprotein, virion, zinc, dna-binding, host-virus interaction, transcription, transcription regulation, zinc binding, hhcc motif, viral protein, recombination
• Biological source: Maedi visna virus (MVV); More
• Cellular location: Nucleus: O75475
• Total number of polymer chains: 12
• Total formula weight: 217391.00

Authors

Hare, S.,Labeja, A.,Cherepanov, P. (deposition date: 2009-06-04, release date: 2009-07-28, Last modification date: 2023-11-01)

Primary citation

Hare, S.,Di Nunzio, F.,Labeja, A.,Wang, J.,Engelman, A.,Cherepanov, P.
Structural basis for functional tetramerization of lentiviral integrase
Plos Pathog., 5:e1000515-e1000515, 2009

PubMed Abstract: Experimental evidence suggests that a tetramer of integrase (IN) is the protagonist of the concerted strand transfer reaction, whereby both ends of retroviral DNA are inserted into a host cell chromosome. Herein we present two crystal structures containing the N-terminal and the catalytic core domains of maedi-visna virus IN in complex with the IN binding domain of the common lentiviral integration co-factor LEDGF. The structures reveal that the dimer-of-dimers architecture of the IN tetramer is stabilized by swapping N-terminal domains between the inner pair of monomers poised to execute catalytic function. Comparison of four independent IN tetramers in our crystal structures elucidate the basis for the closure of the highly flexible dimer-dimer interface, allowing us to model how a pair of active sites become situated for concerted integration. Using a range of complementary approaches, we demonstrate that the dimer-dimer interface is essential for HIV-1 IN tetramerization, concerted integration in vitro, and virus infectivity. Our structures moreover highlight adaptable changes at the interfaces of individual IN dimers that allow divergent lentiviruses to utilize a highly-conserved, common integration co-factor.

PubMed: 19609359
DOI: 10.1371/journal.ppat.1000515

Experimental method

X-RAY DIFFRACTION (3.28 Å)