摘要：

We report the crystal structure, at 2.5 Å resolution, of a truncated human \{EGFR\} ectodomain bound to TGFα. TGFα 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 TGFα: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 \{CR1\} 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.

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