Summary information and primary citation
- PDB-id
- 6dks; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- transcription-DNA
- Method
- X-ray (2.78 Å)
- Summary
- Structure of the rbpj-sharp-DNA repressor complex
- Reference
- Yuan Z, VanderWielen BD, Giaimo BD, Pan L, Collins CE, Turkiewicz A, Hein K, Oswald F, Borggrefe T, Kovall RA (2019): "Structural and Functional Studies of the RBPJ-SHARP Complex Reveal a Conserved Corepressor Binding Site." Cell Rep, 26, 845-854.e6. doi: 10.1016/j.celrep.2018.12.097.
- Abstract
- Notch is a conserved signaling pathway that is essential for metazoan development and homeostasis; dysregulated signaling underlies the pathophysiology of numerous human diseases. Receptor-ligand interactions result in gene expression changes, which are regulated by the transcription factor RBPJ. RBPJ forms a complex with the intracellular domain of the Notch receptor and the coactivator Mastermind to activate transcription, but it can also function as a repressor by interacting with corepressor proteins. Here, we determine the structure of RBPJ bound to the corepressor SHARP and DNA, revealing its mode of binding to RBPJ. We tested structure-based mutants in biophysical and biochemical-cellular assays to characterize the role of RBPJ as a repressor, clearly demonstrating that RBPJ mutants deficient for SHARP binding are incapable of repressing transcription of genes responsive to Notch signaling in cells. Altogether, our structure-function studies provide significant insights into the repressor function of RBPJ.
