View source for 1yyh


==Crystal structure of the human Notch 1 ankyrin domain==
<StructureSection load='1yyh' size='340' side='right'caption='[[1yyh]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1yyh]] 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=1YYH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YYH 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]] 1.901&#8491;</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=1yyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yyh OCA], [https://pdbe.org/1yyh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yyh RCSB], [https://www.ebi.ac.uk/pdbsum/1yyh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yyh ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/NOTC1_HUMAN NOTC1_HUMAN] Defects in NOTCH1 are a cause of aortic valve disease 1 (AOVD1) [MIM:[https://omim.org/entry/109730 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.<ref>PMID:16025100</ref> 
== Function ==
[https://www.uniprot.org/uniprot/NOTC1_HUMAN 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).
== 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/yy/1yyh_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1yyh ConSurf].
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== Publication Abstract from PubMed ==
The Notch receptor is part of a highly conserved signalling system of central importance to animal development. Its ANK (ankyrin) domain is required for Notch-mediated signal transduction. The crystal structure of the human Notch 1 ANK domain was solved by molecular replacement at 1.9 A (1 A=0.1 nm) resolution, and it shows that the features identified in the Drosophila homologue are conserved. The domain has six of the seven ANK repeats predicted from sequence. The putative first repeat, which has only part of the consensus and a long insertion, is disordered in both molecules in the asymmetric unit, possibly due to the absence of the RAM (RBPJkappa-associated molecule) region N-terminal to it. The exposed hydrophobic core is involved in intermolecular interactions in the crystal. Evolutionary trace analysis identified several residues that map to the hairpins of the structure and may be of functional importance. Based on the Notch 1 ANK structure and analysis of homologous Notch ANK sequences, we predict two possible binding sites on the domain: one on the concave surface of repeat 2 and the other below the hairpins of repeats 6-7.

High-resolution crystal structure of the human Notch 1 ankyrin domain.,Ehebauer MT, Chirgadze DY, Hayward P, Martinez Arias A, Blundell TL Biochem J. 2005 Nov 15;392(Pt 1):13-20. PMID:16011479<ref>PMID:16011479</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 1yyh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Blundell TL]]
[[Category: Chirgadze DY]]
[[Category: Ehebauer MT]]
[[Category: Hayward P]]
[[Category: Martinez-Arias A]]