View source for 7sye


==Cryo-EM structure of the extracellular module of the full-length EGFR bound to EGF. "tips-separated" conformation==
<StructureSection load='7sye' size='340' side='right'caption='[[7sye]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7sye]] 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=7SYE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SYE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#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=7sye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sye OCA], [https://pdbe.org/7sye PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sye RCSB], [https://www.ebi.ac.uk/pdbsum/7sye PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sye ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that couples the binding of extracellular ligands, such as EGF and transforming growth factor-alpha (TGF-alpha), to the initiation of intracellular signaling pathways. EGFR binds to EGF and TGF-alpha with similar affinity, but generates different signals from these ligands. To address the mechanistic basis of this phenomenon, we have carried out cryo-EM analyses of human EGFR bound to EGF and TGF-alpha. We show that the extracellular module adopts an ensemble of dimeric conformations when bound to either EGF or TGF-alpha. The two extreme states of this ensemble represent distinct ligand-bound quaternary structures in which the membrane-proximal tips of the extracellular module are either juxtaposed or separated. EGF and TGF-alpha differ in their ability to maintain the conformation with the membrane-proximal tips of the extracellular module separated, and this conformation is stabilized preferentially by an oncogenic EGFR mutation. Close proximity of the transmembrane helices at the junction with the extracellular module has been associated previously with increased EGFR activity. Our results show how EGFR can couple the binding of different ligands to differential modulation of this proximity, thereby suggesting a molecular mechanism for the generation of ligand-sensitive differential outputs in this receptor family.

A molecular mechanism for the generation of ligand-dependent differential outputs by the epidermal growth factor receptor.,Huang Y, Ognjenovic J, Karandur D, Miller K, Merk A, Subramaniam S, Kuriyan J Elife. 2021 Nov 30;10:e73218. doi: 10.7554/eLife.73218. PMID:34846302<ref>PMID:34846302</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 7sye" style="background-color:#fffaf0;"></div>

==See Also==
*[[Epidermal growth factor|Epidermal growth factor]]
*[[Epidermal growth factor receptor 3D structures|Epidermal growth factor receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Huang Y]]
[[Category: Karandur D]]
[[Category: Kuriyan J]]
[[Category: Merk A]]
[[Category: Miller K]]
[[Category: Ognjenovic J]]
[[Category: Subramaniam S]]