A protein composed of the external domain of the epidermal growth factor (EGF) receptor is secreted by A431 human tumor cells. The soluble receptor protein was isolated in bulk quantities from cell culture supernatants. It has an intact ligand binding site, exists in a 93-kDa monomeric form, and does not undergo oligomerization upon ligand binding; thus the receptor dimerization reported for the EGF holoreceptor appears not to be a function of its external domain. The unique system of a physiological soluble receptor was utilized for a crystallization study. Crystals were obtained but only in the presence of the ligand. They contained (in equimolar amounts) receptor as well as EGF. The crystals belong to the tetragonal space group P4(3)2(1)2 or P4(1)2(1)2 with unit cell dimensions a = b = 118 A, c = 202 A. The packing density parameter was 3.55 A3/dalton, indicating the asymmetric unit to consist of one receptor-ligand complex.
