Structure, mechanics, and binding mode heterogeneity of LEDGF/p75–DNA nucleoprotein complexes revealed by scanning force microscopy
- 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.
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| Author: | Willem Vanderlinden, Jan LipfertORCiDGND, Jonas Demeulemeester, Zeger Debyser, Steven De Feyter |
|---|---|
| URN: | urn:nbn:de:bvb:384-opus4-1143982 |
| Frontdoor URL | https://opus.bibliothek.uni-augsburg.de/opus4/114398 |
| ISSN: | 2040-3364OPAC |
| ISSN: | 2040-3372OPAC |
| Parent Title (English): | Nanoscale |
| Publisher: | Royal Society of Chemistry (RSC) |
| Type: | Article |
| Language: | English |
| Year of first Publication: | 2014 |
| Publishing Institution: | Universität Augsburg |
| Release Date: | 2024/07/29 |
| Volume: | 6 |
| Issue: | 9 |
| First Page: | 4611 |
| Last Page: | 4619 |
| DOI: | https://doi.org/10.1039/c4nr00022f |
| Institutes: | Mathematisch-Naturwissenschaftlich-Technische Fakultät |
| Mathematisch-Naturwissenschaftlich-Technische Fakultät / Institut für Physik | |
| Mathematisch-Naturwissenschaftlich-Technische Fakultät / Institut für Physik / Lehrstuhl für Experimentalphysik I | |
| Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
| Licence (German): |  CC-BY 3.0: Creative Commons - Namensnennung (mit Print on Demand) |
