Title: HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells
Authors: Cherepanov, Peter
Maertens, Goedele
Proost, Paul
Devreese, Bart
Van Beeumen, Jozef
Engelborghs, Yves
De Clercq, Erik
Debyser, Zeger # ×
Issue Date: Jan-2003
Series Title: Journal of Biological Chemistry vol:278 issue:1 pages:372-381
Abstract: We studied human immunodeficiency virus, type 1 (HIV-1) integrase (IN) complexes derived from nuclei of human cells stably expressing the viral protein from a synthetic gene. We show that in the nuclear extracts IN exists as part of a large distinct complex with an apparent Stokes radius of 61 A, which dissociates upon dilution yielding a core molecule of 41 A. We isolated the IN complexes from cells expressing FLAG-tagged IN and demonstrated that the 41 A core is a tetramer of IN, whereas 61 A molecules are composed of IN tetramers associated with a cellular protein with an apparent molecular mass of 76 kDa. This novel integrase interacting protein was found to be identical to lens epithelium-derived growth factor (LEDGF/p75), a protein implicated in regulation of gene expression and cellular stress response. HIV-1 IN and LEDGF co-localized in the nuclei of human cells stably expressing IN. Furthermore, recombinant LEDGF robustly enhanced strand transfer activity of HIV-1 IN in vitro. Our findings indicate that the minimal IN molecule in human cells is a homotetramer, suggesting that at least an octamer of IN is required to accomplish coordinated integration of both retroviral long terminal repeats and that LEDGF is a cellular factor involved in this process.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Molecular Immunology (Rega Institute)
Biochemistry, Molecular and Structural Biology Section
Laboratory of Virology and Chemotherapy (Rega Institute)
Molecular Virology and Gene Therapy
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science