NMR investigation of FOXO4-DNA interaction for discriminating target and non-target DNA sequences.
| Autor: | Kang D; Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea., Yang MJ; Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea., Cheong HK; Ochang Center, Korea Basic Science Institute, Chungcheongbuk-do, 28119, Republic of Korea., Park CJ; Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea. cjpark@gist.ac.kr. |
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| Jazyk: | angličtina |
| Zdroj: | Communications biology [Commun Biol] 2024 Nov 01; Vol. 7 (1), pp. 1425. Date of Electronic Publication: 2024 Nov 01. |
| DOI: | 10.1038/s42003-024-07133-1 |
| Abstrakt: | Forkhead box O4 (FOXO4), a human transcription factor, recognizes target DNA through its forkhead domain (FHD) while maintaining comparable binding affinity to non-target DNA. The conserved region 3 (CR3), a transactivation domain, modulates DNA binding kinetics to FHD and contributes to target DNA selection, but the underlying mechanism of this selection remains elusive. Using paramagnetic relaxation enhancement analysis, we observed a minor state of CR3 close to FHD in the presence of non-target DNA, a state absent when FHD interacts with target DNA. This minor state suggests that CR3 effectively masks the non-target DNA-binding interface on FHD. The interaction weakens significantly under high salt concentration, implying that CR3 or high salt concentrations can modulate electrostatic interactions with non-target DNA. Our 15 N relaxation measurements revealed FHD's flexibility with non-target DNA and increased rigidity with target DNA binding. Our findings offer insights into the role of FOXO4 as a transcription initiator. (© 2024. The Author(s).) |
| Databáze: | MEDLINE |
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