Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	A molecular mechanism for the generation of ligand-dependent differential outputs by the epidermal growth factor receptor.
Journal, issue, pages	Elife, Vol. 10, Year 2021
Publish date	Nov 30, 2021
Authors	Yongjian Huang / Jana Ognjenovic / Deepti Karandur / Kate Miller / Alan Merk / Sriram Subramaniam / John Kuriyan /
PubMed Abstract	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-α (TGF-α), to the initiation ...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-α (TGF-α), to the initiation of intracellular signaling pathways. EGFR binds to EGF and TGF-α 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-α. We show that the extracellular module adopts an ensemble of dimeric conformations when bound to either EGF or TGF-α. 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-α 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.
External links	Elife / PubMed:34846302 / PubMed Central
Methods	EM (single particle)
Resolution	3.1 - 3.6 Å
Structure data	25522 7syd EMDB-25522, PDB-7syd: Cryo-EM structure of the extracellular module of the full-length EGFR bound to EGF "tips-juxtaposed" conformation Method: EM (single particle) / Resolution: 3.1 Å 25523 7sye EMDB-25523, PDB-7sye: Cryo-EM structure of the extracellular module of the full-length EGFR bound to EGF. "tips-separated" conformation Method: EM (single particle) / Resolution: 3.3 Å 25558 7sz0 EMDB-25558, PDB-7sz0: Cryo-EM structure of the extracellular module of the full-length EGFR L834R bound to EGF. "tips-juxtaposed" conformation Method: EM (single particle) / Resolution: 3.3 Å 25559 7sz1 EMDB-25559, PDB-7sz1: Cryo-EM structure of the extracellular module of the full-length EGFR L834R bound to EGF. "tips-separated" conformation Method: EM (single particle) / Resolution: 3.4 Å 25561 7sz5 EMDB-25561, PDB-7sz5: Cryo-EM structure of the extracellular module of the full-length EGFR bound to TGF-alpha "tips-separated" conformation Method: EM (single particle) / Resolution: 3.6 Å 25563 7sz7 EMDB-25563, PDB-7sz7: Cryo-EM structure of the extracellular module of the full-length EGFR bound to TGF-alpha. "tips-juxtaposed" conformation Method: EM (single particle) / Resolution: 3.4 Å
Source	homo sapiens (human)
Keywords	SIGNALING PROTEIN / receptor tyrosine kinases / epidermal growth factor receptor / SIGNALING PROTEIN/RECEPTOR / SIGNALING PROTEIN-RECEPTOR complex / Transferase