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1mox

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(New page: 200px<br /> <applet load="1mox" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mox, resolution 2.5&Aring;" /> '''Crystal Structure of...)
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[[Image:1mox.gif|left|200px]]<br />
 
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<applet load="1mox" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1mox, resolution 2.5&Aring;" />
 
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'''Crystal Structure of Human Epidermal Growth Factor Receptor (residues 1-501) in complex with TGF-alpha'''<br />
 
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==Overview==
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==Crystal Structure of Human Epidermal Growth Factor Receptor (residues 1-501) in complex with TGF-alpha==
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We report the crystal structure, at 2.5 A resolution, of a truncated human, EGFR ectodomain bound to TGFalpha. TGFalpha interacts with both L1 and L2, domains of EGFR, making many main chain contacts with L1 and interacting, with L2 via key conserved residues. The results indicate how EGFR family, members can bind a family of highly variable ligands. In the 2:2, TGFalpha:sEGFR501 complex, each ligand interacts with only one receptor, molecule. There are two types of dimers in the asymmetric unit: a, head-to-head dimer involving contacts between the L1 and L2 domains and a, back-to-back dimer dominated by interactions between the CR1 domains of, each receptor. Based on sequence conservation, buried surface area, and, mutagenesis experiments, the back-to-back dimer is favored to be, biologically relevant.
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<StructureSection load='1mox' size='340' side='right'caption='[[1mox]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1mox]] is a 4 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=1MOX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MOX 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]] 2.5&#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=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PT:PLATINUM+(II)+ION'>PT</scene></td></tr>
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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=1mox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mox OCA], [https://pdbe.org/1mox PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mox RCSB], [https://www.ebi.ac.uk/pdbsum/1mox PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mox 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/mo/1mox_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=1mox ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases 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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*[[Epidermal growth factor receptor 3D structures|Epidermal growth factor receptor 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1MOX is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, PT, CD and CL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1MOX OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha., Garrett TP, McKern NM, Lou M, Elleman TC, Adams TE, Lovrecz GO, Zhu HJ, Walker F, Frenkel MJ, Hoyne PA, Jorissen RN, Nice EC, Burgess AW, Ward CW, Cell. 2002 Sep 20;110(6):763-73. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12297049 12297049]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Transferase]]
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[[Category: Adams TE]]
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[[Category: Adams, T.E.]]
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[[Category: Burgess AW]]
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[[Category: Burgess, A.W.]]
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[[Category: Elleman TC]]
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[[Category: Elleman, T.C.]]
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[[Category: Frenkel MJ]]
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[[Category: Frenkel, M.J.]]
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[[Category: Garrett TPJ]]
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[[Category: Garrett, T.P.J.]]
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[[Category: Hoyne PA]]
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[[Category: Hoyne, P.A.]]
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[[Category: Jorissen RN]]
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[[Category: Jorissen, R.N.]]
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[[Category: Lou M]]
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[[Category: Lou, M.]]
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[[Category: Lovrecz GO]]
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[[Category: Lovrecz, G.O.]]
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[[Category: McKern NM]]
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[[Category: McKern, N.M.]]
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[[Category: Nice EC]]
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[[Category: Nice, E.C.]]
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[[Category: Walker F]]
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[[Category: Walker, F.]]
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[[Category: Ward CW]]
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[[Category: Ward, C.W.]]
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[[Category: Zhu H-J]]
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[[Category: Zhu, H.J.]]
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[[Category: CD]]
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[[Category: CL]]
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[[Category: NAG]]
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[[Category: PT]]
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[[Category: complex]]
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[[Category: egfr]]
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[[Category: growth factor]]
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[[Category: receptor]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:13:28 2007''
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Current revision

Crystal Structure of Human Epidermal Growth Factor Receptor (residues 1-501) in complex with TGF-alpha

PDB ID 1mox

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