Abstract
Notch receptors transduce essential developmental signals between neighboring cells by forming a complex that leads to transcription of target genes upon activation. We report here the crystal structure of a Notch transcriptional activation complex containing the ankyrin domain of human Notch1 (ANK), the transcription factor CSL on cognate DNA, and a polypeptide from the coactivator Mastermind-like-1 (MAML-1). Together, CSL and ANK create a groove to bind the MAML-1 polypeptide as a kinked, 70 A helix. The composite binding surface likely restricts the recruitment of MAML proteins to promoters on which Notch:CSL complexes have been preassembled, ensuring tight transcriptional control of Notch target genes.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Crystallography, X-Ray
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation
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Humans
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Immunoglobulin J Recombination Signal Sequence-Binding Protein / genetics
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Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism*
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Macromolecular Substances
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Models, Molecular
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Molecular Sequence Data
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Nucleic Acid Conformation
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Promoter Regions, Genetic
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Protein Structure, Quaternary*
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Receptor, Notch1 / chemistry*
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Receptor, Notch1 / genetics
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Receptor, Notch1 / metabolism*
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Sequence Alignment
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Trans-Activators
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Transcription Factors
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Transcription, Genetic*
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Transcriptional Activation*
Substances
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DNA-Binding Proteins
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Immunoglobulin J Recombination Signal Sequence-Binding Protein
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MAML1 protein, human
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Macromolecular Substances
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Nuclear Proteins
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RBPJ protein, human
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Receptor, Notch1
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Trans-Activators
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Transcription Factors