Crystal Structure of the CSL-Notch-Mastermind Ternary Complex Bound to DNA
Open accessAbstract
Notch signaling mediates communication between cells and is essential for proper embryonic patterning and development. CSL is a DNA binding transcription factor that regulates transcription of Notch target genes by interacting with coregulators. Transcriptional activation requires the displacement of corepressors from CSL by the intracellular portion of the receptor Notch (NotchIC) and the recruitment of the coactivator protein Mastermind to the complex. Here we report the 3.1 A structure of the ternary complex formed by CSL, NotchIC, and Mastermind bound to DNA. As expected, the RAM domain of Notch interacts with the beta trefoil domain of CSL; however, the C-terminal domain of CSL has an unanticipated central role in the interface formed with the Notch ankyrin repeats and Mastermind. Ternary complex formation induces a substantial conformational change within CSL, suggesting a molecular mechanism for the conversion of CSL from a repressor to an activator.
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Upon ligand binding, the Notch intracellular domain, which includes a 111-amino acid intrinsically disordered region, binds the transcription factor CSL, the coactivator Mastermind, and Notch target DNA.
“Upon ligand binding, the Notch intracellular domain, which includes a 111-amino acid intrinsically disordered region, binds the transcription factor CSL (an acronym of human and mouse CBF1/RBPJ-κ, Drosophila Suppressor of Hairless, and C. elegans Lag-1), the coactivator Mastermind, and Notch target DNA [251].”
From Intrinsically disordered proteins play diverse roles in cell signaling (2022) · cites this paper as [251]
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- Authors
- Wilson, J. J., & Kovall, R. A.
- Affiliations
- University of Cincinnati (US)
- Corresponding author
- Kovall, Rhett A.
- ORCID
- Kovall, Rhett A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 124
- Issue
- 5
- Pages
- 985-996
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2086059239
- Cited by
- 371
- References
- 51
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 17 · 2023: 27 · 2022: 13 · 2021: 18 · 2020: 18 · 2019: 17 · 2018: 19 · 2017: 19 · 2016: 16 · 2015: 13 · 2014: 18 · 2013: 11 · 2012: 18
- FWCI
- 11.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2726 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- CSL, Notch signaling, Mastermind, ternary complex, DNA binding, transcriptional activation, ankyrin repeats, transcriptional coregulators, protein-DNA complex structure
- MeSH terms
- Amino Acid Sequence, Animals, DNA, DNA-Binding Proteins, Humans, Models, Molecular, Molecular Sequence Data, Nuclear Proteins, Repressor Proteins, Transcription Factors, Transcription, Genetic, Signal Transduction, Transcriptional Activation, Trans-Activators, Sequence Alignment, Protein Structure, Secondary, Protein Structure, Tertiary, Crystallography, X-Ray, Macromolecular Substances, Receptors, Notch, Static Electricity
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