1ivo
From Proteopedia
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==Crystal Structure of the Complex of Human Epidermal Growth Factor and Receptor Extracellular Domains.== | ==Crystal Structure of the Complex of Human Epidermal Growth Factor and Receptor Extracellular Domains.== | ||
| - | <StructureSection load='1ivo' size='340' side='right' caption='[[1ivo]], [[Resolution|resolution]] 3.30Å' scene=''> | + | <StructureSection load='1ivo' size='340' side='right'caption='[[1ivo]], [[Resolution|resolution]] 3.30Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1ivo]] is a 4 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[1ivo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The June 2010 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Epidermal Growth Factor Receptor'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2010_6 10.2210/rcsb_pdb/mom_2010_6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IVO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IVO FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |
| - | <tr><td class="sblockLbl"><b> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ivo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ivo OCA], [https://pdbe.org/1ivo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ivo RCSB], [https://www.ebi.ac.uk/pdbsum/1ivo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ivo ProSAT], [https://www.topsan.org/Proteins/RSGI/1ivo TOPSAN]</span></td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </table> |
| - | <table> | + | |
== Disease == | == Disease == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN] Defects in EGFR are associated with lung cancer (LNCR) [MIM:[https://omim.org/entry/211980 211980]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. |
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN] Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.<ref>PMID:7657591</ref> <ref>PMID:11602604</ref> <ref>PMID:12873986</ref> <ref>PMID:10805725</ref> <ref>PMID:11116146</ref> <ref>PMID:11483589</ref> <ref>PMID:17115032</ref> <ref>PMID:21258366</ref> <ref>PMID:12297050</ref> <ref>PMID:12620237</ref> <ref>PMID:15374980</ref> <ref>PMID:19560417</ref> <ref>PMID:20837704</ref> Isoform 2 may act as an antagonist of EGF action.<ref>PMID:7657591</ref> <ref>PMID:11602604</ref> <ref>PMID:12873986</ref> <ref>PMID:10805725</ref> <ref>PMID:11116146</ref> <ref>PMID:11483589</ref> <ref>PMID:17115032</ref> <ref>PMID:21258366</ref> <ref>PMID:12297050</ref> <ref>PMID:12620237</ref> <ref>PMID:15374980</ref> <ref>PMID:19560417</ref> <ref>PMID:20837704</ref> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/iv/1ivo_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/iv/1ivo_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | + | </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=1ivo ConSurf]. |
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
| + | <div class="pdbe-citations 1ivo" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| - | *[[Epidermal Growth Factor Receptor|Epidermal Growth Factor Receptor]] | ||
*[[Epidermal growth factor|Epidermal growth factor]] | *[[Epidermal growth factor|Epidermal growth factor]] | ||
| + | *[[Epidermal growth factor receptor 3D structures|Epidermal growth factor receptor 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Epidermal Growth Factor Receptor]] | [[Category: Epidermal Growth Factor Receptor]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: RCSB PDB Molecule of the Month]] | [[Category: RCSB PDB Molecule of the Month]] | ||
| - | + | [[Category: Fukai S]] | |
| - | [[Category: Fukai | + | [[Category: Ishitani R]] |
| - | [[Category: Ishitani | + | [[Category: Kim JH]] |
| - | [[Category: Kim | + | [[Category: Nureki O]] |
| - | [[Category: Nureki | + | [[Category: Ogiso H]] |
| - | [[Category: Ogiso | + | [[Category: Saito K]] |
| - | + | [[Category: Shirouzu M]] | |
| - | [[Category: Saito | + | [[Category: Yamanaka M]] |
| - | [[Category: Shirouzu | + | [[Category: Yokoyama S]] |
| - | [[Category: Yamanaka | + | |
| - | [[Category: Yokoyama | + | |
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Current revision
Crystal Structure of the Complex of Human Epidermal Growth Factor and Receptor Extracellular Domains.
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