title: Structure, mechanics, and binding mode heterogeneity of LEDGF/p75-DNA nucleoprotein complexes revealed by scanning force microscopy.
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.
authors.affiliation: Department of Chemistry, Laboratory of Photochemistry and Spectroscopy, Division of Molecular Imaging and Photonics, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium. willem.vanderlinden@chem.kuleuven.be steven.defeyter@chem.kuleuven.be.
authors.forename: Willem
authors.initials: W
authors.lastname: Vanderlinden
authors.forename: Jan
authors.initials: J
authors.lastname: Lipfert
authors.forename: Jonas
authors.initials: J
authors.lastname: Demeulemeester
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Steven
authors.initials: S
authors.lastname: De Feyter
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018625:Microscopy, Atomic Force; D009698:Nucleoproteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009698:Nucleoproteins; D011993:Recombinant Fusion Proteins; C119380:lens epithelium-derived growth factor; D004247:DNA