Department of Molecular, Cell and Cancer Biology
Amino Acids, Peptides, and Proteins | Biochemistry | Biophysics | Enzymes and Coenzymes | Molecular Biology | Structural Biology
Intrinsically disordered transcription factor transactivation domains (TADs) function through structural plasticity, adopting ordered conformations when bound to transcriptional co-regulators. Many transcription factors contain a negative regulatory domain (NRD) that suppresses recruitment of transcriptional machinery through autoregulation of the TAD. We report the solution structure of an autoinhibited NRD-TAD complex within FoxM1, a critical activator of mitotic gene expression. We observe that while both the FoxM1 NRD and TAD are primarily intrinsically disordered domains, they associate and adopt a structured conformation. We identify how Plk1 and Cdk kinases cooperate to phosphorylate FoxM1, which releases the TAD into a disordered conformation that then associates with the TAZ2 or KIX domains of the transcriptional co-activator CBP. Our results support a mechanism of FoxM1 regulation in which the TAD undergoes switching between disordered and different ordered structures.
Cdk, Plk1, human, intrinsically disordered proteins, molecular biophysics, nuclear magnetic resonance, structural biology, transcription factors
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Copyright © 2019, Marceau et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
DOI of Published Version
Elife. 2019 May 28;8. pii: 46131. doi: 10.7554/eLife.46131. Link to article on publisher's site
Marceau AH, Brison CM, Nerli S, Arsenault HE, McShan AC, Chen E, Lee H, Benanti JA, Sgourakis NG, Rubin SM. (2019). An order-to-disorder structural switch activates the FoxM1 transcription factor. Open Access Articles. https://doi.org/10.7554/eLife.46131. Retrieved from https://escholarship.umassmed.edu/oapubs/3844
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