The solution structure of human epidermal growth factor

The epidermal growth factors (EGFs)^1-3 are powerful mitogens for a wide variety of cells in culture⁴; human EGF (hEGF), known as urogastrone, also inhibits gastric acid secretion in vivo¹. The transforming growth factors (TGF-α) are related to the EGF family both in sequence⁵ and activity^6,7 and EGF-like sequences are often observed in a wide range of functionally unrelated proteins⁸. Attempts to examine the structure of EGF by diffraction methods have not yet succeeded because of difficulties with crystallization. We report here a three-dimensional structure of a biologically active derivative (residues 1-48) of the 53-residue human EGF. An analysis of high resolution ¹H nuclear magnetic resonance (NMR) spectra was used together with a combination of distance geometry, restrained energy minimization and restrained molecular dynamics methods. The three-dimensional structure provides a basis for understanding the properties of EGFs and for predicting the structures of homologous sequences in other proteins.