The 3D structures of epidermal growth factor (EGF from mouse and human) and type a transforming growth factor (TGFα from human) in solution were studied by two-dimensional proton NMR spectroscopy. The pH of the samples were pH 2-3 for EGF and pH 4.9 for TGFα. The backbone foldings of EGF and TGFα are similar to each other, which is consistent with the fact that they compete for binding to the same receptor. The dynamical properties, however, are different; TGFα is unusually flexible at acidic pHs. We found that a proline at residue 29 is responsible for this difference. By means of 2D NMR pH titration experiment, the resonance assignment of mouse EGF at pH 6.8 was accomplished. On the basis of the assignment, the 3D structure of mouse EGF at the physiological pH was calculated. Then, the conformation of mouse EGF bound to micelles at pH 6.8 was determined. EGF interacts with micelles through the C-terminal tail region, which adopts an amphiphilic structure on binding to micelles. We propose a “mitten” model to describe the interaction mode of EGF/TGFα with the receptor.
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