ITEM METADATA RECORD
Title: Identification of the LEDGF/p75 Binding Site in HIV-1 Integrase
Authors: Busschots, Katrien
Voet, Arnout
De Maeyer, Marc
Rain, Jean-Christophe
Emiliani, Stéphane
Benarous, Richard
Desender, Linda
Debyser, Zeger ×
Christ, Frauke #
Issue Date: Feb-2007
Series Title: Journal of Molecular Biology vol:365 issue:5 pages:1480-1492
Abstract: Lens epithelium-derived growth factor (LEDGF)/p75 is an important cellular co-factor for human immunodeficiency virus (HIV) replication. We originally identified LEDGF/p75 as a binding partner of integrase (IN) in human cells. The interaction has been mapped to the integrase-binding domain (IBD) of LEDGF/p75 located in the C-terminal part. We have subsequently shown that IN carrying the Q168A mutation remains enzymatically active but is impaired for interaction with LEDGF/p75. To map the integrase/LEDGF interface in more detail, we have now identified and characterized two regions within the enzyme involved in the interaction with LEDGF/p75. The first region centers around residues W131 and W132 while the second extends from I161 up to E170. For the different IN mutants the interaction with LEDGF/p75 and the enzymatic activities were determined. IN(W131A), IN(I161A), IN(R166A), IN(Q168A) and IN(E170A) are impaired for interaction with LEDGF/p75, but retain 3' processing and strand transfer activities. Due to impaired integration, an HIV-1 strain containing the W131A mutation in IN displays reduced replication capacity, whereas virus carrying IN(Q168A) is replication defective. Comparison of the wild-type IN-LEDGF/p75 co-crystal structure with that of the modelled structure of the IN(Q168A) and IN(W131A) mutant integrases corroborated our experimental data.
URI: 
ISSN: 0022-2836
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Virology and Gene Therapy
Biochemistry, Molecular and Structural Biology Section
Biochemistry, Kulak (-)
× 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