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Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha


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
2002-09-20
CELL
Journal Article
110
6
763-773
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.
CELL PRESS
NUCLEAR-MAGNETIC-RESONANCE; FACTOR EGF RECEPTOR; SIGNALING NETWORK; ATOMIC-STRUCTURE; HEREGULIN-ALPHA; BINDING DOMAIN; COMPLEX; LIGAND; RECOGNITION; ECTODOMAIN
10.1016/S0092-8674(02)00940-6
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Creation Date 2002-09-20 12:00:00