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	Ligand regulation and function of preformed EGFR dimers.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 123, Issue 30, Page e2602436123, Year 2026
Publish date	Jul 28, 2026
Authors	Yuhong Zuo / Hillel T Schwartz / Kahlil Walker / Long Han / Paul W Sternberg / Kathryn M Ferguson /
PubMed Abstract	Receptor tyrosine kinases (RTKs) are key therapeutic targets in cancer, diabetes, and other diseases. With only one transmembrane α-helix-compared with seven in G-protein-coupled receptors-RTKs are ...Receptor tyrosine kinases (RTKs) are key therapeutic targets in cancer, diabetes, and other diseases. With only one transmembrane α-helix-compared with seven in G-protein-coupled receptors-RTKs are thought to be activated by ligand-induced dimerization. Complicating this view, however, one of the best-studied RTKs, the insulin receptor (IR), forms allosterically regulated covalent dimers. Moreover, noncovalent "preformed" dimers have frequently been reported for the sequence-related epidermal growth factor receptor (EGFR), one of the first RTKs for which ligand-induced dimerization was described. Here, we describe a detailed structural view of a preformed EGFR dimer. Using cryo-EM, we describe how the EGFR (LET-23) dimerizes without ligand. We show that preformed dimer formation modulates ligand sensitivity in vivo, but is not required for signaling itself. We also elucidate substantial ligand-induced conformational changes in LET-23 required for signaling. Our structures reveal unexpected similarities between regulation of LET-23 and the IR, suggesting that LET-23 may represent an evolutionary "missing link" between the IR and EGFR families. In the absence of ligand, intermolecular interactions within preformed receptor dimers hold the extracellular juxtamembrane regions far apart to separate the intracellular kinase domains so that they remain inactive. Ligand binding disrupts these interactions to remove the restraints on the kinase domains, which then can associate to become activated. Our analysis further suggests a unified model for the allosteric activation of preformed RTK dimers that has important implications for understanding cell-surface EGFR.
External links	Proc Natl Acad Sci U S A / PubMed:42475585 / PubMed Central
Methods	EM (single particle)
Resolution	2.37 - 4.0 Å
Structure data	73275 9yor EMDB-73275, PDB-9yor: Cryo-EM structure of a preformed dimer of the C. elegans EGFR (LET-23) extracellular region Method: EM (single particle) / Resolution: 2.9 Å 73276 9yos EMDB-73276, PDB-9yos: Cryo-EM structure of an active dimer of the C. elegans EGFR (LET-23) extracellular region bound to LIN-3 Method: EM (single particle) / Resolution: 2.37 Å 73277 9yot EMDB-73277, PDB-9yot: Cryo-EM structure of an inactive dimer of the C. elegans EGFR (LET-23) extracellular region bound to LIN-3. Method: EM (single particle) / Resolution: 2.81 Å 73278 9you EMDB-73278, PDB-9you: Cryo-EM structure of a weak dimer of the C. elegans EGFR (LET-23) extracellular region with a domain IV loop deletion Method: EM (single particle) / Resolution: 4.0 Å 73279 9yov EMDB-73279, PDB-9yov: Cryo-EM structure of an active dimer of the C. elegans EGFR (LET-23) extracellular region with a domain IV loop deletion bound to LIN-3. Method: EM (single particle) / Resolution: 3.36 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose
Source	caenorhabditis elegans (invertebrata) drosophila melanogaster (fruit fly)
Keywords	SIGNALING PROTEIN / Receptor Tyrosine Kinase / epidermal growth factor receptor / preformed dimer / LET-23 / ligand-bound dimer