3LTF

Crystal Structure of the Drosophila Epidermal Growth Factor Receptor ectodomain in complex with Spitz

Summary for 3LTF

• Entry DOI: 10.2210/pdb3ltf/pdb
• Related: 3I2T 3LTG
• Descriptor: Epidermal growth factor receptor, Protein spitz, alpha-D-mannopyranose-(1-4)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 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 (Fruit fly); More
• Total number of polymer chains: 4
• Total formula weight: 152414.94

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

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: 20723758
DOI: 10.1016/j.cell.2010.07.015

Experimental method

X-RAY DIFFRACTION (3.2 Å)