6OSW

An order-to-disorder structural switch activates the FoxM1 transcription factor

Summary for 6OSW

• Entry DOI: 10.2210/pdb6osw/pdb
• NMR Information: BMRB: 30608
• Descriptor: Forkhead box M1 (2 entities in total)
• Functional Keywords: transcription factor, cell cycle, negative regulatory domain, transactivation domain
• Biological source: Danio rerio (Zebrafish); More
• Total number of polymer chains: 2
• Total formula weight: 16465.67

Authors

Marceau, A.H.,Rubin, S.M.,Nerli, S.,McShane, A.C.,Sgourakis, N.G. (deposition date: 2019-05-02, release date: 2019-05-29, Last modification date: 2024-05-15)

Primary citation

Marceau, A.H.,Brison, C.M.,Nerli, S.,Arsenault, H.E.,McShan, A.C.,Chen, E.,Lee, H.W.,Benanti, J.A.,Sgourakis, N.G.,Rubin, S.M.
An order-to-disorder structural switch activates the FoxM1 transcription factor.
Elife, 8:-, 2019

PubMed Abstract: 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.

PubMed: 31134895
DOI: 10.7554/eLife.46131

Experimental method

SOLUTION NMR