title: Polypeptide chain fold of human transforming growth factor alpha analogous to those of mouse and human epidermal growth factors as studied by two-dimensional 1H NMR.
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 degrees 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.
authors: Department of Molecular Physiology, Tokyo Metropolitan Institute of Medical Science, Japan.
authors: D
authors: D
authors: Kohda
authors: I
authors: I
authors: Shimada
authors: T
authors: T
authors: Miyake
authors: T
authors: T
authors: Fuwa
authors: F
authors: F
authors: Inagaki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006801:Humans; D006859:Hydrogen; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D015291:Transforming Growth Factors / Q000378:metabolism*
chemical_list: D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D006859:Hydrogen