Ribbon diagram of the crystal structure of an EGFR homodimer in complex with two EGF ligands (from pdb code 1IVO).

<p>A The subdomains I, II, III and IV of both receptors are colored pink, orange, cyan and purple, respectively. Held between domains I and III of each receptor are the EGF ligands colored red and their disulfide bridges yellow. The three main interactions sites between EGF and EGFR are outlined (1, 2 and 3). The interaction site 3 between C-terminal part of EGF and domain III of EGFR is magnified. This binding site is composed by two different kinds of interactions: hydrophobic interactions between Leu47 (EGF) and Leu382, Phe412, and Ile438 (EGFR), and the formation of hydrogen bonds with Gln384 side chain of EGFR and carbonyl and amide groups of Gln43 and Arg45, respectively, of EGF. All side chains of residues responsible for these interactions are shown in different colors depending on the type of interaction. B Ribbon diagram and amino acid sequence of EGF. The C-terminal part of the molecule is highlighted in black and the side chain of Leu47 is shown in orange in the ribbon diagram. The nucleotides that encode these 8 amino acids were removed from the encoding sequence to construct the EGF truncated form (EGFt).