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Structure of the Su(H)-Hairless-DNA Repressor ComplexStructure of the Su(H)-Hairless-DNA Repressor Complex
Structural highlights
Function[MALE_ECO57] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides (By similarity). [SUH_DROME] Transcriptional regulator that plays a central role in Notch signaling, a signaling pathway involved in cell-cell communication that regulates a broad spectrum of cell-fate determinations. Binds directly the 5'-GTGRGAR-3' DNA consensus sequence, which is present in the regulatory region of several genes. Required for neurogenesis in imaginal disks. Acts as a transcriptional repressor when it is not associated with Notch proteins. When associated with some Notch protein, it acts as a transcriptional activator that activates transcription of Notch target genes. Specifically binds to the immunoglobulin kappa-type J segment recombination signal sequence. Required for transcription of Sim. Also functions independently of Notch pathway, in the development of the bristle sensory organ precursor cell.[1] [2] [3] [HLES_DROME] Is a potent antagonist of neurogenic gene activity during sensory organ development. The expression of distinct cell fates by the trichogen (shaft) / tormogen (socket) sister cell pair depends on the level of H activity. A certain threshold level of H activity is required, below which both sister cells adopt the tormogen fate.[4] [5] Publication Abstract from PubMedNotch is a conserved signaling pathway that specifies cell fates in metazoans. Receptor-ligand interactions induce changes in gene expression, which is regulated by the transcription factor CBF1/Su(H)/Lag-1 (CSL). CSL interacts with coregulators to repress and activate transcription from Notch target genes. While the molecular details of the activator complex are relatively well understood, the structure-function of CSL-mediated repressor complexes is poorly defined. In Drosophila, the antagonist Hairless directly binds Su(H) (the fly CSL ortholog) to repress transcription from Notch targets. Here, we determine the X-ray structure of the Su(H)-Hairless complex bound to DNA. Hairless binding produces a large conformational change in Su(H) by interacting with residues in the hydrophobic core of Su(H), illustrating the structural plasticity of CSL molecules to interact with different binding partners. Based on the structure, we designed mutants in Hairless and Su(H) that affect binding, but do not affect formation of the activator complex. These mutants were validated in vitro by isothermal titration calorimetry and yeast two- and three-hybrid assays. Moreover, these mutants allowed us to solely characterize the repressor function of Su(H) in vivo. Structure and Function of the Su(H)-Hairless Repressor Complex, the Major Antagonist of Notch Signaling in Drosophila melanogaster.,Yuan Z, Praxenthaler H, Tabaja N, Torella R, Preiss A, Maier D, Kovall RA PLoS Biol. 2016 Jul 12;14(7):e1002509. doi: 10.1371/journal.pbio.1002509., eCollection 2016 Jul. PMID:27404588[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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