2fo1
From Proteopedia
Crystal Structure of the CSL-Notch-Mastermind ternary complex bound to DNA
Structural highlights
FunctionLAG1_CAEEL Transcriptional regulator that plays a central role in lin-12/Notch and glp-1/Notch signaling pathways, involved in cell-cell communication that regulate a broad spectrum of cell-fate determinations (PubMed:8625826). Binds directly to the 5'-[A/G]TGGGAA-3' DNA consensus sequence, which is present in the regulatory region of several genes (PubMed:8625826, PubMed:18706403, PubMed:23615264, PubMed:15297877, PubMed:32196486, PubMed:21737278). Acts as a transcriptional repressor when it is not associated with Notch proteins (By similarity). When in a complex with a Notch intracellular domain (NICD) product of lin-12/Notch or glp-1/Notch, and transcription regulator lag-3, it may act as a transcriptional activator that activates transcription of target genes(PubMed:18381292, PubMed:10830967, PubMed:32196486, PubMed:9003776). Probably represses or activates transcription via the recruitment of chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins, respectively (By similarity). Autonomously required in the germline for the stem cell fate, acting in the glp-1-dependent transcriptional activation of genes, including lst-1 and sygl-1 (PubMed:32196486). Involved in cell-fate specification during reproductive system development, by positively autoregulating its own expression, in response to lin-12/Notch signaling (PubMed:23615264, PubMed:32839181). Plays a role in Notch-dependent induction of left-right asymmetry in interneurons and motoneurons (PubMed:21737278). May repress expression of hlh-6, in a lin-12/Notch-independent manner (PubMed:18706403).[UniProtKB:P28159][1] [2] [3] [4] [5] [6] [7] [8] [9] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedNotch signaling mediates communication between cells and is essential for proper embryonic patterning and development. CSL is a DNA binding transcription factor that regulates transcription of Notch target genes by interacting with coregulators. Transcriptional activation requires the displacement of corepressors from CSL by the intracellular portion of the receptor Notch (NotchIC) and the recruitment of the coactivator protein Mastermind to the complex. Here we report the 3.1 A structure of the ternary complex formed by CSL, NotchIC, and Mastermind bound to DNA. As expected, the RAM domain of Notch interacts with the beta trefoil domain of CSL; however, the C-terminal domain of CSL has an unanticipated central role in the interface formed with the Notch ankyrin repeats and Mastermind. Ternary complex formation induces a substantial conformational change within CSL, suggesting a molecular mechanism for the conversion of CSL from a repressor to an activator. Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA.,Wilson JJ, Kovall RA Cell. 2006 Mar 10;124(5):985-96. PMID:16530045[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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