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| | <StructureSection load='5uk5' size='340' side='right'caption='[[5uk5]], [[Resolution|resolution]] 2.51Å' scene=''> | | <StructureSection load='5uk5' size='340' side='right'caption='[[5uk5]], [[Resolution|resolution]] 2.51Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5uk5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UK5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UK5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5uk5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UK5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=XYS:XYLOPYRANOSE'>XYS</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.506Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=XYS:XYLOPYRANOSE'>XYS</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xl1|4xl1]], [[4xlw|4xlw]], [[4cc0|4cc0]], [[4d0e|4d0e]], [[2vj3|2vj3]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5uk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uk5 OCA], [https://pdbe.org/5uk5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uk5 RCSB], [https://www.ebi.ac.uk/pdbsum/5uk5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uk5 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Notch1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Jag1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5uk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uk5 OCA], [http://pdbe.org/5uk5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uk5 RCSB], [http://www.ebi.ac.uk/pdbsum/5uk5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uk5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NOTC1_RAT 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.<ref>PMID:11182080</ref> [[http://www.uniprot.org/uniprot/JAG1_RAT JAG1_RAT]] Ligand for multiple Notch receptors and involved in the mediation of Notch signaling. May be involved in cell-fate decisions during hematopoiesis. Enhances fibroblast growth factor-induced angiogenesis (in vitro). Seems to be involved in early and late stages of mammalian cardiovascular development. Inhibits myoblast differentiation. May regulate fibroblast growth factor-induced angiogenesis. | + | [https://www.uniprot.org/uniprot/NOTC1_RAT 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.<ref>PMID:11182080</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Garcia, K C]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Luca, V C]] | + | [[Category: Garcia KC]] |
| - | [[Category: Delta]] | + | [[Category: Luca VC]] |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Jagged]]
| + | |
| - | [[Category: Notch]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| 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: | , , , , , , |
| 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.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tanigaki K, Nogaki F, Takahashi J, Tashiro K, Kurooka H, Honjo T. Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate. Neuron. 2001 Jan;29(1):45-55. PMID:11182080
- ↑ Luca VC, Kim BC, Ge C, Kakuda S, Wu D, Roein-Peikar M, Haltiwanger RS, Zhu C, Ha T, Garcia KC. Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity. Science. 2017 Mar 2. pii: eaaf9739. doi: 10.1126/science.aaf9739. PMID:28254785 doi:http://dx.doi.org/10.1126/science.aaf9739
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