3NBN

Crystal structure of a dimer of Notch Transcription Complex trimers on HES1 DNA

Summary for 3NBN

• Entry DOI: 10.2210/pdb3nbn/pdb
• Descriptor: Recombining binding protein suppressor of hairless, Neurogenic locus notch homolog protein 1, Mastermind-like protein 1, ... (5 entities in total)
• Functional Keywords: promoter regions, notch1, csl, rbpj, mastermind, transcription factors, transcription, transcriptional activation, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q06330; Cell membrane ; Single-pass type I membrane protein . Notch 1 intracellular domain: Nucleus : P46531; Nucleus speckle : Q92585
• Total number of polymer chains: 8
• Total formula weight: 192047.56

Authors

Arnett, K.L.,Blacklow, S.C. (deposition date: 2010-06-03, release date: 2010-11-03, Last modification date: 2024-10-30)

Primary citation

Arnett, K.L.,Hass, M.,McArthur, D.G.,Ilagan, M.X.,Aster, J.C.,Kopan, R.,Blacklow, S.C.
Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes.
Nat.Struct.Mol.Biol., 17:1312-1317, 2010

PubMed Abstract: Ligand-induced proteolysis of Notch produces an intracellular effector domain that transduces essential signals by regulating the transcription of target genes. This function relies on the formation of transcriptional activation complexes that include intracellular Notch, a Mastermind co-activator and the transcription factor CSL bound to cognate DNA. These complexes form higher-order assemblies on paired, head-to-head CSL recognition sites. Here we report the X-ray structure of a dimeric human Notch1 transcription complex loaded on the paired site from the human HES1 promoter. The small interface between the Notch ankyrin domains could accommodate DNA bending and untwisting to allow a range of spacer lengths between the two sites. Cooperative dimerization occurred on the human and mouse Hes5 promoters at a sequence that diverged from the CSL-binding consensus at one of the sites. These studies reveal how promoter organizational features control cooperativity and, thus, the responsiveness of different promoters to Notch signaling.

PubMed: 20972443
DOI: 10.1038/nsmb.1938

Experimental method

X-RAY DIFFRACTION (3.45 Å)