Polypeptide Chain Fold of Human Transforming Growth Factor α Analogous to Those of Mouse and Human Epidermal Growth Factors As Studied by Two-Dimensional 1H NMR

Daisuke Kohda, Ichio Shimada, Tetsuo Miyake, Toru Fuwa, Fuyuhiko Inagaki

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The 1H NMR spectrum of human transforming growth factor α (TGF-α) 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-α in solution (pH 4.9, 28 °C) were determined to satisfy the upper limits of proton-proton distances derived from nuclear Overhauser effect experiments. Although human TGF-α 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-α is well characterized by the “mitten model” previously proposed for mouse EGF. The gross shape of the TGF-α molecule resembles a mitten. TGF-α 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.

Original languageEnglish
Pages (from-to)953-958
Number of pages6
JournalBiochemistry
Volume28
Issue number3
DOIs
Publication statusPublished - Jan 1 1989

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Transforming Growth Factors
Nuclear magnetic resonance
Peptides
Epidermal Growth Factor
Protons
Intercellular Signaling Peptides and Proteins
Amino Acid Sequence Homology
Molecules
EGF Family of Proteins
Proton Magnetic Resonance Spectroscopy
Amino Acids
Experiments

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Polypeptide Chain Fold of Human Transforming Growth Factor α Analogous to Those of Mouse and Human Epidermal Growth Factors As Studied by Two-Dimensional 1H NMR. / Kohda, Daisuke; Shimada, Ichio; Miyake, Tetsuo; Fuwa, Toru; Inagaki, Fuyuhiko.

In: Biochemistry, Vol. 28, No. 3, 01.01.1989, p. 953-958.

Research output: Contribution to journalArticle

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