7sye

Cryo-EM structure of the extracellular module of the full-length EGFR bound to EGF. "tips-separated" conformation

spinqualitylabelsall models 7sye, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7sye is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Epidermal growth factor Epidermal growth factor receptor 3D structures

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