Title: Structure, mechanics, and binding mode heterogeneity of LEDGF/p75-DNA nucleoprotein complexes revealed by scanning force microscopy
Authors: Vanderlinden, Willem
Lipfert, Jan
Demeulemeester, Jonas
Debyser, Zeger
De Feyter, Steven # ×
Issue Date: Apr-2014
Publisher: RSC Publishing
Series Title: Nanoscale vol:6 issue:9 pages:4611-4619
Abstract: LEDGF/p75 is a transcriptional coactivator implicated in the pathogenesis of AIDS and leukemia. In these contexts, LEDGF/p75 acts as a cofactor by tethering protein cargo to transcriptionally active regions in the human genome. Our study - based on scanning force microscopy (SFM) imaging - is the first to provide structural information on the interaction of LEDGF/p75 with DNA. Two novel approaches that allow obtaining insights into the DNA conformation inside nucleoprotein complexes revealed (1) that LEDGF/p75 can bind at least in three different binding modes, (2) how DNA topology and protein dimerization affect these binding modes, and (3) geometrical and mechanical aspects of the nucleoprotein complexes. These structural and mechanical details will help us to better understand the cellular mechanisms of LEDGF/p75 as a transcriptional coactivator and as a cofactor in disease.
ISSN: 2040-3364
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Virology and Gene Therapy
× corresponding author
# (joint) last author

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