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Structural Basis of Notch Pathway Repression

Notch signaling is a form of cell-to-cell communication, in which extracellular receptor-ligand interactions ultimately result in changes in gene expression. The Notch pathway is highly conserved from the model organism Drosophila melanogaster to humans, and mutations that affect Notch pathway components can lead to human disease, such as certain types of cancers and birth defects. The transcription factor CSL regulates gene expression in response to Notch pathway signaling. Yuan et al. now present the X-ray structure of the complex between the fruit fly version of CSL (Suppressor of Hairless), and its antagonist, Hairless, revealing a novel binding mode and unanticipated structural plasticity. In this image, CSL is represented as a gray surface with the residues that contact Hairless colored orange; Hairless is colored yellow, and the DNA of the target gene is colored purple and pink.

Image Credit: 10.1371/journal.pbio.1002509.g002