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Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes.

Nam Y, Sliz P, Song L, Aster JC, Blacklow SC.

Biological and Biomedical Sciences Graduate Program in the Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA.

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:
PMID: 16530044 [PubMed - indexed for MEDLINE]