6DKS

Structure of the Rbpj-SHARP-DNA Repressor Complex

Summary for 6DKS

• Entry DOI: 10.2210/pdb6dks/pdb
• Related PRD ID: PRD_900001
• Descriptor: DNA (5'-D(*AP*AP*TP*CP*TP*TP*TP*CP*CP*CP*AP*CP*AP*GP*T)-3'), DNA (5'-D(*TP*TP*AP*CP*TP*GP*TP*GP*GP*GP*AP*AP*AP*GP*A)-3'), Recombining binding protein suppressor of hairless, ... (5 entities in total)
• Functional Keywords: notch signaling, rbpjk, sharp, mint, csl, transport-dna binding-dna complex, transcription-dna complex, transcription/dna
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 8
• Total formula weight: 203472.04

Authors

Kovall, R.A.,VanderWielen, B.D.,Yuan, Z. (deposition date: 2018-05-30, release date: 2019-01-02, Last modification date: 2023-10-11)

Primary citation

Yuan, Z.,VanderWielen, B.D.,Giaimo, B.D.,Pan, L.,Collins, C.E.,Turkiewicz, A.,Hein, K.,Oswald, F.,Borggrefe, T.,Kovall, R.A.
Structural and Functional Studies of the RBPJ-SHARP Complex Reveal a Conserved Corepressor Binding Site.
Cell Rep, 26:845-854.e6, 2019

PubMed 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.

PubMed: 30673607
DOI: 10.1016/j.celrep.2018.12.097

Experimental method

X-RAY DIFFRACTION (2.78 Å)