Overlapping characteristics of weak interactions of two transcriptional regulators with WDR5.

Autor: Ahmad M; Department of Physics, Syracuse University, 201 Physics Building, Syracuse, NY 13244-1130, USA., Imran A; Department of Physics, Syracuse University, 201 Physics Building, Syracuse, NY 13244-1130, USA., Movileanu L; Department of Physics, Syracuse University, 201 Physics Building, Syracuse, NY 13244-1130, USA; Department of Biomedical and Chemical Engineering, Syracuse University, 329 Link Hall, Syracuse, NY 13244, USA; The BioInspired Institute, Syracuse University, Syracuse, NY 13244, USA. Electronic address: lmovilea@syr.edu.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Feb; Vol. 258 (Pt 2), pp. 128969. Date of Electronic Publication: 2023 Dec 27.
DOI: 10.1016/j.ijbiomac.2023.128969
Abstrakt: The WD40 repeat protein 5 (WDR5) is a nuclear hub that critically influences gene expression by interacting with transcriptional regulators. Utilizing the WDR5 binding motif (WBM) site, WDR5 interacts with the myelocytomatosis (MYC), an oncoprotein transcription factor, and the retinoblastoma-binding protein 5 (RbBP5), a scaffolding element of an epigenetic complex. Given the clinical significance of these protein-protein interactions (PPIs), there is a pressing necessity for a quantitative assessment of these processes. Here, we use biolayer interferometry (BLI) to examine interactions of WDR5 with consensus peptide ligands of MYC and RbBP5. We found that both interactions exhibit relatively weak affinities arising from a fast dissociation process. Remarkably, live-cell imaging identified distinctive WDR5 localizations in the absence and presence of full-length binding partners. Although WDR5 tends to accumulate within nucleoli, WBM-mediated interactions with MYC and RbBP5 require their localization outside nucleoli. We utilize fluorescence resonance energy transfer (FRET) microscopy to confirm these weak interactions through a low FRET efficiency of the MYC-WDR5 and RbBP5-WDR5 complexes in living cells. In addition, we evaluate the impact of peptide and small-molecule inhibitors on these interactions. These outcomes form a fundamental basis for further developments to clarify the multitasking role of the WBM binding site of WDR5.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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