3ltg is a 3 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[EGFR_DROME] Binds to four ligands: Spitz, Gurken, Vein and Argos, which is an antagonist. Transduces the signal through the ras-raf-MAPK pathway. Involved in a myriad of developmental decisions. Critical for the proliferation of imaginal tissues, and for the determination of both the antero-posterior and dorso-ventral polarities of the oocyte. In the embryo, plays a role in the establishment of ventral cell fates, maintenance of amnioserosa and ventral neuroectodermal cells, germ band retraction, cell fate specification in the central nervous system and production of cuticle. Required for embryonic epithelial tissue repair.[1] [SPITZ_DROME] Ligand for the EGF receptor (Gurken). Involved in a number of unrelated developmental choices, for example, dorsal-ventral axis formation, glial migration, sensory organ determination, and muscle development. It is required for photoreceptor determination.[2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structural basis for negative cooperativity in growth factor binding to an EGF receptor.,Alvarado D, Klein DE, Lemmon MA Cell. 2010 Aug 20;142(4):568-79. PMID:20723758[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Geiger JA, Carvalho L, Campos I, Santos AC, Jacinto A. Hole-in-one mutant phenotypes link EGFR/ERK signaling to epithelial tissue repair in Drosophila. PLoS One. 2011;6(11):e28349. doi: 10.1371/journal.pone.0028349. Epub 2011 Nov 29. PMID:22140578 doi:https://dx.doi.org/10.1371/journal.pone.0028349
↑Freeman M. The spitz gene is required for photoreceptor determination in the Drosophila eye where it interacts with the EGF receptor. Mech Dev. 1994 Oct;48(1):25-33. PMID:7833286
↑Alvarado D, Klein DE, Lemmon MA. Structural basis for negative cooperativity in growth factor binding to an EGF receptor. Cell. 2010 Aug 20;142(4):568-79. PMID:20723758 doi:10.1016/j.cell.2010.07.015
