3LTG
Crystal structure of the Drosophila Epidermal Growth Factor Receptor ectodomain complexed with a low affinity Spitz mutant
Summary for 3LTG
| Entry DOI | 10.2210/pdb3ltg/pdb |
| Related | 3CA7 3I2T 3LTF |
| Descriptor | Epidermal growth factor receptor, Protein spitz (2 entities in total) |
| Functional Keywords | receptor-ligand complex ectodomain cysteine rich domain egf domain, atp-binding, kinase, nucleotide-binding, receptor, transferase, tyrosine-protein kinase, cell membrane, developmental protein, differentiation, disulfide bond, egf-like domain, endoplasmic reticulum, glycoprotein, golgi apparatus, membrane, neurogenesis, transmembrane, transferase-transferase regulator complex, transferase/transferase regulator |
| Biological source | Drosophila melanogaster More |
| Cellular location | Membrane; Single-pass type I membrane protein: P04412 Cell membrane; Single-pass type I membrane protein: Q01083 |
| Total number of polymer chains | 3 |
| Total formula weight | 141954.69 |
| Authors | Alvarado, D.,Klein, D.E.,Lemmon, M.A. (deposition date: 2010-02-15, release date: 2010-08-25, Last modification date: 2024-10-30) |
| Primary citation | Alvarado, D.,Klein, D.E.,Lemmon, M.A. Structural basis for negative cooperativity in growth factor binding to an EGF receptor. Cell(Cambridge,Mass.), 142:568-579, 2010 Cited by PubMed Abstract: Transmembrane signaling by the epidermal growth factor receptor (EGFR) involves ligand-induced dimerization and allosteric regulation of the intracellular tyrosine kinase domain. Crystallographic studies have shown how ligand binding induces dimerization of the EGFR extracellular region but cannot explain the "high-affinity" and "low-affinity" classes of cell-surface EGF-binding sites inferred from curved Scatchard plots. From a series of crystal structures of the Drosophila EGFR extracellular region, we show here how Scatchard plot curvature arises from negatively cooperative ligand binding. The first ligand-binding event induces formation of an asymmetric dimer with only one bound ligand. The unoccupied site in this dimer is structurally restrained, leading to reduced affinity for binding of the second ligand, and thus negative cooperativity. Our results explain the cell-surface binding characteristics of EGF receptors and suggest how individual EGFR ligands might stabilize distinct dimeric species with different signaling properties. PubMed: 20723758DOI: 10.1016/j.cell.2010.07.015 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.4 Å) |
Structure validation
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