5uk5

Complex of Notch1(EGF8-12) bound to Jagged1(N-EGF3)

spinqualitylabelsall models 5uk5, resolution 2.51Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5uk5 is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.506Å Ligands: BGC, CA, FUC, MES, MLY, NAG, XYS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NOTC1_RAT Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. May be important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, may function as a receptor for neuronal DNER and may be involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May enhance HIF1A function by sequestering HIF1AN away from HIF1A (By similarity). Acts instructively to control the cell fate determination of CNS multipotent progenitor cells, resulting in astroglial induction and neuron/oligodendrocyte suppression. Publication Abstract from PubMed Notch receptor activation initiates cell fate decisions, and is distinctive in its reliance on mechanical force and protein glycosylation. The 2.5 angstrom crystal structure of the extracellular interacting regions of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein. O-Linked fucose modifications on Notch1 EGF domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch domains are favored in binding to Jag1 compared to those that bind to the Delta-like 4 ligand. Jag1 undergoes conformational changes upon Notch binding, exhibiting catch bond behavior that prolongs interactions in the range of forces required for Notch activation. This mechanism enables cellular forces to regulate binding, discriminate amongst Notch ligands and potentiate Notch signaling. Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity.,Luca VC, Kim BC, Ge C, Kakuda S, Wu D, Roein-Peikar M, Haltiwanger RS, Zhu C, Ha T, Garcia KC Science. 2017 Mar 2. pii: eaaf9739. doi: 10.1126/science.aaf9739. PMID:28254785 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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