Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha
- Author(s)
- Garrett, TPJ; McKern, NM; Lou, MZ; Elleman, TC; Adams, TE; Lovrecz, GO; Zhu, HJ; Walker, F; Frenkel, MJ; Hoyne, PA; Jorissen, RN; Nice, EC; Burgess, AW; Ward, CW;
- Details
- Publication Year 2002-09-20,Volume 110,Issue #6,Page 763-773
- Journal Title
- CELL
- Publication Type
- Journal Article
- Abstract
- We report the crystal structure, at 2.5 Angstrom resolution, of a truncated human EGFR ectodomain bound to TGFalpha. TGFalpha interacts with both L1 and L2 domains of EGFR, making many main chain contacts with L1 and interacting with L2 via key conserved residues. The results indicate how EGFR family members can bind a family of highly variable ligands. In the 2:2 TGFalpha:sEGFR501 complex, each ligand interacts with only one receptor molecule. There are two types of dimers; in the asymmetric unit: a head-to-head dimer involving contacts between the L1 and L2 domains and a back-to-back dimer dominated by interactions between the CRI domains of each receptor. Based on sequence conservation, buried surface area, and mutagenesis experiments, the back-to-back dimer is favored to be biologically relevant.
- Publisher
- CELL PRESS
- Keywords
- NUCLEAR-MAGNETIC-RESONANCE; FACTOR EGF RECEPTOR; SIGNALING NETWORK; ATOMIC-STRUCTURE; HEREGULIN-ALPHA; BINDING DOMAIN; COMPLEX; LIGAND; RECOGNITION; ECTODOMAIN
- Publisher's Version
- https://doi.org/10.1016/S0092-8674(02)00940-6
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2002-09-20 12:00:00