Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes.
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.
Nam
Yunsun
Y
Biological and Biomedical Sciences Graduate Program in the Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA.
Sliz
Piotr
P
Song
Luyan
L
Aster
Jon C
JC
Blacklow
Stephen C
SC
D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism*; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D020836:Protein Structure, Quaternary; D051881:Receptor, Notch1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015534:Trans-Activators; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C430872:MAML1 protein, human; D046911:Macromolecular Substances; D009687:Nuclear Proteins; C497570:RBPJ protein, human; D051881:Receptor, Notch1; D015534:Trans-Activators; D014157:Transcription Factors