2m20

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[[Image:2m20.jpg|left|200px]]
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==EGFR transmembrane - juxtamembrane (TM-JM) segment in bicelles: MD guided NMR refined structure.==
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<StructureSection load='2m20' size='340' side='right' caption='[[2m20]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2m20]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M20 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M20 FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EGFR, ERBB, ERBB1, HER1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2m20 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m20 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2m20 RCSB], [http://www.ebi.ac.uk/pdbsum/2m20 PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN]] Defects in EGFR are associated with lung cancer (LNCR) [MIM:[http://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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[[http://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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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How the epidermal growth factor receptor (EGFR) activates is incompletely understood. The intracellular portion of the receptor is intrinsically active in solution, and to study its regulation, we measured autophosphorylation as a function of EGFR surface density in cells. Without EGF, intact EGFR escapes inhibition only at high surface densities. Although the transmembrane helix and the intracellular module together suffice for constitutive activity even at low densities, the intracellular module is inactivated when tethered on its own to the plasma membrane, and fluorescence cross-correlation shows that it fails to dimerize. NMR and functional data indicate that activation requires an N-terminal interaction between the transmembrane helices, which promotes an antiparallel interaction between juxtamembrane segments and release of inhibition by the membrane. We conclude that EGF binding removes steric constraints in the extracellular module, promoting activation through N-terminal association of the transmembrane helices.
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{{STRUCTURE_2m20| PDB=2m20 | SCENE= }}
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Conformational Coupling across the Plasma Membrane in Activation of the EGF Receptor.,Endres NF, Das R, Smith AW, Arkhipov A, Kovacs E, Huang Y, Pelton JG, Shan Y, Shaw DE, Wemmer DE, Groves JT, Kuriyan J Cell. 2013 Jan 31;152(3):543-56. doi: 10.1016/j.cell.2012.12.032. PMID:23374349<ref>PMID:23374349</ref>
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===EGFR transmembrane - juxtamembrane (TM-JM) segment in bicelles: MD guided NMR refined structure.===
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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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{{ABSTRACT_PUBMED_23374349}}
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==See Also==
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*[[Epidermal Growth Factor Receptor|Epidermal Growth Factor Receptor]]
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==About this Structure==
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== References ==
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[[2m20]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M20 OCA].
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Arkhipov, A.]]
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[[Category: Arkhipov, A]]
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[[Category: Das, R.]]
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[[Category: Das, R]]
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[[Category: Endres, N F.]]
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[[Category: Endres, N F]]
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[[Category: Groves, J T.]]
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[[Category: Groves, J T]]
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[[Category: Huang, Y.]]
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[[Category: Huang, Y]]
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[[Category: Kovacs, E.]]
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[[Category: Kovacs, E]]
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[[Category: Kuriyan, J.]]
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[[Category: Kuriyan, J]]
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[[Category: Pelton, J G.]]
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[[Category: Pelton, J G]]
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[[Category: Shan, Y.]]
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[[Category: Shan, Y]]
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[[Category: Shaw, D E.]]
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[[Category: Shaw, D E]]
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[[Category: Smith, A.]]
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[[Category: Smith, A]]
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[[Category: Wemmer, D E.]]
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[[Category: Wemmer, D E]]
[[Category: Cell signaling]]
[[Category: Cell signaling]]
[[Category: Juxtamembrane]]
[[Category: Juxtamembrane]]
[[Category: Signaling protein]]
[[Category: Signaling protein]]
[[Category: Transmembrane]]
[[Category: Transmembrane]]

Revision as of 08:45, 26 November 2014

EGFR transmembrane - juxtamembrane (TM-JM) segment in bicelles: MD guided NMR refined structure.

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