NDLI: HIV-1 Integrase Forms Stable Tetramers and Associates with LEDGF/p75 Protein in Human Cells

Content Provider	Journal of Biological Chemistry (JBC)
Author	Cherepanov, Peter Maertens, Goedele Proost, Paul Devreese, Bart Beeumen, Jozef Van Engelborghs, Yves Clercq, Erik De Debyser, Zeger
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 Å, which dissociates upon dilution yielding a core molecule of 41 Å. We isolated the IN complexes from cells expressing FLAG-tagged IN and demonstrated that the 41 Å core is a tetramer of IN, whereas 61 Å 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.
Related Links	http://www.jbc.org/content/278/1/372.abstract
Ending Page	381
Starting Page	372
Page Count	10
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	1
Volume Number	278
DOI	10.1074/jbc.M209278200
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2003-01-03
Access Restriction	Open
Subject Keyword	Human immunodeficiency virus (HIV) 3-[(3-cholamidopropyl)dimethyl-ammonio]propanesulfonate (CHAPS) 3,3′-dithiobis[sulfosuccinimidyl propionate] (DTSSP) Hepatoma-derived growth factor (HDGF) Integrase (IN) FLAG-tagged IN (INf) Synthetic integrase gene (INs) Lens epithelium-derived growth factor (LEDGF) Long terminal repeat (LTR) Mass spectrometry (MS) Polyethylene glycol (PEG) Preintegration complex (PIC) 1,4-piperazinediethanesulfonic acid (Pipes) Barrier-to-autointegration factor (BAF) Integrase interactor 1 (Ini1) Liquid chromatography (LC) Catalytic subunit of DNA-dependent protein kinase (DNA PKcs) DNA: REPLICATION REPAIR AND RECOMBINATION
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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