6DKS

Structure of the Rbpj-SHARP-DNA Repressor Complex

6DKS の概要

• エントリーDOI: 10.2210/pdb6dks/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: 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)
• 機能のキーワード: notch signaling, rbpjk, sharp, mint, csl, transport-dna binding-dna complex, transcription-dna complex, transcription/dna
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 203472.04

構造登録者

Kovall, R.A.,VanderWielen, B.D.,Yuan, Z. (登録日: 2018-05-30, 公開日: 2019-01-02, 最終更新日: 2023-10-11)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.78 Å)