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5fm9

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Revision as of 07:25, 6 May 2020

human Notch 1, EGF 4-7

Structural highlights

5fm9 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5fma
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[NOTC1_HUMAN] Defects in NOTCH1 are a cause of aortic valve disease 1 (AOVD1) [MIM:109730]. A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome.^[1]

Function

[NOTC1_HUMAN] 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 normal lymphocyte function. In altered form, may contribute to transformation or progression in some T-cell neoplasms. Involved in the maturation of both CD4+ and CD8+ cells in the thymus. 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).

Publication Abstract from PubMed

The Notch receptor is a key component of a core metazoan signaling pathway activated by Delta/Serrate/Lag-2 ligands expressed on an adjacent cell. This results in a short-range signal with profound effects on cell-fate determination, cell proliferation, and cell death. Key to understanding receptor function is structural knowledge of the large extracellular portion of Notch which contains multiple repeats of epidermal growth factor (EGF)-like domains. Here we investigate the EGF4-13 region of human Notch1 (hN1) using a multidisciplinary approach. Ca(2+)-binding measurements, X-ray crystallography, {(1)H}-(15)N heteronuclear nuclear Overhauser effects, and residual dipolar couplings support a non-linear organization for the EGF4-13 region with a rigid, bent conformation for EGF4-7 and a single flexible linkage between EGF9 and EGF10. These data allow us to construct an informed model for EGF10-13 which, in conjunction with comparative binding studies, demonstrates that EGF10 has an important role in determining Notch receptor sensitivity to Dll-4.

Non-Linear and Flexible Regions of the Human Notch1 Extracellular Domain Revealed by High-Resolution Structural Studies.,Weisshuhn PC, Sheppard D, Taylor P, Whiteman P, Lea SM, Handford PA, Redfield C Structure. 2016 Apr 5;24(4):555-66. doi: 10.1016/j.str.2016.02.010. Epub 2016 Mar, 17. PMID:26996961^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Garg V, Muth AN, Ransom JF, Schluterman MK, Barnes R, King IN, Grossfeld PD, Srivastava D. Mutations in NOTCH1 cause aortic valve disease. Nature. 2005 Sep 8;437(7056):270-4. Epub 2005 Jul 17. PMID:16025100 doi:10.1038/nature03940
↑ Weisshuhn PC, Sheppard D, Taylor P, Whiteman P, Lea SM, Handford PA, Redfield C. Non-Linear and Flexible Regions of the Human Notch1 Extracellular Domain Revealed by High-Resolution Structural Studies. Structure. 2016 Apr 5;24(4):555-66. doi: 10.1016/j.str.2016.02.010. Epub 2016 Mar, 17. PMID:26996961 doi:http://dx.doi.org/10.1016/j.str.2016.02.010

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5fm9"

@@ Line 1: / Line 1: @@
 ==human Notch 1, EGF 4-7==
-<StructureSection load='5fm9' size='340' side='right' caption='[[5fm9]], [[Resolution|resolution]] 2.92&Aring;' scene=''>
+<StructureSection load='5fm9' size='340' side='right'caption='[[5fm9]], [[Resolution|resolution]] 2.92&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5fm9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FM9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FM9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5fm9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FM9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5FM9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fma|5fma]]</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=5fm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fm9 OCA], [http://pdbe.org/5fm9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fm9 RCSB], [http://www.ebi.ac.uk/pdbsum/5fm9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fm9 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5fm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fm9 OCA], [http://pdbe.org/5fm9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fm9 RCSB], [http://www.ebi.ac.uk/pdbsum/5fm9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fm9 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 26: / Line 26: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Handford, P A]]
 [[Category: Lea, S M]]

5fm9

From Proteopedia

Revision as of 07:25, 6 May 2020

human Notch 1, EGF 4-7

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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