View source for 2vj2


==Human Jagged-1, domains DSL and EGFs1-3==
<StructureSection load='2vj2' size='340' side='right'caption='[[2vj2]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2vj2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VJ2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLT:D-MALATE'>MLT</scene></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=2vj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vj2 OCA], [https://pdbe.org/2vj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vj2 RCSB], [https://www.ebi.ac.uk/pdbsum/2vj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vj2 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/JAG1_HUMAN JAG1_HUMAN] Defects in JAG1 are the cause of Alagille syndrome type 1 (ALGS1) [MIM:[https://omim.org/entry/118450 118450]. Alagille syndrome is an autosomal dominant multisystem disorder defined clinically by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. There are characteristic facial features and less frequent clinical involvement of the renal and vascular systems.<ref>PMID:9207788</ref> <ref>PMID:9207787</ref> <ref>PMID:9585603</ref> <ref>PMID:10220506</ref> <ref>PMID:10533065</ref> <ref>PMID:11058898</ref> <ref>PMID:11157803</ref> <ref>PMID:11139247</ref> <ref>PMID:11180599</ref> <ref>PMID:12442286</ref> <ref>PMID:12497640</ref> <ref>PMID:15712272</ref> <ref>PMID:16575836</ref>   Defects in JAG1 are a cause of tetralogy of Fallot (TOF) [MIM:[https://omim.org/entry/187500 187500]. TOF is a congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. This condition results in a blue baby at birth due to inadequate oxygenation. Surgical correction is emergent.<ref>PMID:9207787</ref> <ref>PMID:11152664</ref> 
== Function ==
[https://www.uniprot.org/uniprot/JAG1_HUMAN JAG1_HUMAN] Ligand for multiple Notch receptors and involved in the mediation of Notch signaling. May be involved in cell-fate decisions during hematopoiesis. Seems to be involved in early and late stages of mammalian cardiovascular development. Inhibits myoblast differentiation (By similarity). Enhances fibroblast growth factor-induced angiogenesis (in vitro).<ref>PMID:9462510</ref> <ref>PMID:18660822</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vj/2vj2_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vj2 ConSurf].
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== Publication Abstract from PubMed ==
The Notch receptor and its ligands are key components in a core metazoan signaling pathway that regulates the spatial patterning, timing and outcome of many cell-fate decisions. Ligands contain a disulfide-rich Delta/Serrate/LAG-2 (DSL) domain required for Notch trans-activation or cis-inhibition. Here we report the X-ray structure of a receptor binding region of a Notch ligand, the DSL-EGF3 domains of human Jagged-1 (J-1(DSL-EGF3)). The structure reveals a highly conserved face of the DSL domain, and we show, by functional analysis of Drosophila melanogster ligand mutants, that this surface is required for both cis- and trans-regulatory interactions with Notch. We also identify, using NMR, a surface of Notch-1 involved in J-1(DSL-EGF3) binding. Our data imply that cis- and trans-regulation may occur through the formation of structurally distinct complexes that, unexpectedly, involve the same surfaces on both ligand and receptor.

A conserved face of the Jagged/Serrate DSL domain is involved in Notch trans-activation and cis-inhibition.,Cordle J, Johnson S, Tay JZ, Roversi P, Wilkin MB, de Madrid BH, Shimizu H, Jensen S, Whiteman P, Jin B, Redfield C, Baron M, Lea SM, Handford PA Nat Struct Mol Biol. 2008 Aug;15(8):849-57. Epub 2008 Jul 27. PMID:18660822<ref>PMID:18660822</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2vj2" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cordle J]]
[[Category: Handford PA]]
[[Category: Johnson S]]
[[Category: Lea SM]]
[[Category: Roversi P]]
[[Category: Tay JZ]]