Polypeptide chain fold of human transforming growth factor .alpha. analogous to those of mouse and human epidermal growth factors as studied by two-dimensional proton NMR

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Abstract
The 1H NMR spectrum of human transforming growth factor .alpha. (TGF-.alpha.) was analyzed almost completely by the sequential assignment method using two-dimensional NMR techniques. On the basis of the nearly complete sequence-specific resonance assignment, secondary and tertiary structures of human TGF-.alpha. in solution (pH 4.9, 28.degree. C) were determined to satisfy the upper limits of proton-proton distances derived from nuclear Overhauser effect experiments. Although human TGF-.alpha. and mouse epidermal growth factor (EGF) share 27% homology in amino acid sequence, the backbone chain folds in the two growth factors are quite similar. The structure and function of TGF-.alpha. is well characterized by the "mitten model" previously proposed for mouse EGF. The gross shape of the TGF-.alpha. molecule resembles a mitten. TGF-.alpha. interacts with the receptor as a mitten would grasp an object. However, there is an appreciable structural difference between the two growth factors in the back of the mitten that is formed by the N-terminal polypeptide segment. This is consistent with the evidence that the backs of these molecules are not involved in the receptor binding.

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