1yy9

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{{Seed}}
 
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[[Image:1yy9.png|left|200px]]
 
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==Structure of the extracellular domain of the epidermal growth factor receptor in complex with the Fab fragment of cetuximab/Erbitux/IMC-C225==
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The line below this paragraph, containing "STRUCTURE_1yy9", creates the "Structure Box" on the page.
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<StructureSection load='1yy9' size='340' side='right'caption='[[1yy9]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1yy9]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. 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=1YY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YY9 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.605&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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{{STRUCTURE_1yy9| PDB=1yy9 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1yy9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yy9 OCA], [https://pdbe.org/1yy9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yy9 RCSB], [https://www.ebi.ac.uk/pdbsum/1yy9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yy9 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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.
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yy/1yy9_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1yy9 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Recent structural studies of epidermal growth factor receptor (EGFR) family extracellular regions have identified an unexpected mechanism for ligand-induced receptor dimerization that has important implications for activation and inhibition of these receptors. Here we describe the 2.8 angstroms resolution X-ray crystal structure of the antigen binding (Fab) fragment from cetuximab (Erbitux), an inhibitory anti-EGFR antibody, in complex with the soluble extracellular region of EGFR (sEGFR). The sEGFR is in the characteristic "autoinhibited" or "tethered" inactive configuration. Cetuximab interacts exclusively with domain III of sEGFR, partially occluding the ligand binding region on this domain and sterically preventing the receptor from adopting the extended conformation required for dimerization. We suggest that both these effects contribute to potent inhibition of EGFR activation.
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===Structure of the extracellular domain of the epidermal growth factor receptor in complex with the Fab fragment of cetuximab/Erbitux/IMC-C225===
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Structural basis for inhibition of the epidermal growth factor receptor by cetuximab.,Li S, Schmitz KR, Jeffrey PD, Wiltzius JJ, Kussie P, Ferguson KM Cancer Cell. 2005 Apr;7(4):301-11. PMID:15837620<ref>PMID:15837620</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1yy9" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_15837620}}, adds the Publication Abstract to the page
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*[[Epidermal growth factor receptor 3D structures|Epidermal growth factor receptor 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 15837620 is the PubMed ID number.
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*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
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== References ==
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{{ABSTRACT_PUBMED_15837620}}
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<references/>
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__TOC__
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==Disease==
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</StructureSection>
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Known disease associated with this structure: Adenocarcinoma of lung, response to tyrosine kinase inhibitor in OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=131550 131550]], Nonsmall cell lung cancer, response to tyrosine kinase inhibitor in OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=131550 131550]], Nonsmall cell lung cancer, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=131550 131550]]
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[[Category: Epidermal Growth Factor Receptor]]
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==About this Structure==
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1YY9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus/homo_sapiens Mus musculus/homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YY9 OCA].
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==Reference==
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Structural basis for inhibition of the epidermal growth factor receptor by cetuximab., Li S, Schmitz KR, Jeffrey PD, Wiltzius JJ, Kussie P, Ferguson KM, Cancer Cell. 2005 Apr;7(4):301-11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15837620 15837620]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Mus musculus/homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Mus musculus]]
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[[Category: Transferase]]
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[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Ferguson, K M.]]
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[[Category: Ferguson KM]]
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[[Category: Jeffrey, P D.]]
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[[Category: Jeffrey PD]]
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[[Category: Kussie, P.]]
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[[Category: Kussie P]]
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[[Category: Li, S.]]
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[[Category: Li S]]
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[[Category: Schmitz, K R.]]
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[[Category: Schmitz KR]]
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[[Category: Wiltzius, J J.W.]]
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[[Category: Wiltzius JJW]]
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[[Category: Antigen:antibody complex]]
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[[Category: Antitumor]]
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[[Category: Cell surface receptor]]
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[[Category: Drug]]
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[[Category: Fab fragment]]
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[[Category: Glycoprotein]]
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[[Category: Tyrosine kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 23:39:42 2008''
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Current revision

Structure of the extracellular domain of the epidermal growth factor receptor in complex with the Fab fragment of cetuximab/Erbitux/IMC-C225

PDB ID 1yy9

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