Recognition of an antiparallel β-sheet structure of human epidermal growth factor by its receptor Site-directed mutagenesis studies of Ala-30 and Asn-32

Hiroshi Koide, Yutaka Muto, Hidefumi Kasai, Kumiko Hoshi, Hiromi Takusari, Kaoru Kohri, Seizo Takahashi, Tetsuyuki Sasaki, Ken ichi Tsukumo, Tetsuo Miyake, Tohru Fuwa, Tatsuo Miyazawa, Shigeyuki Yokoyama

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Abstract

The Ala-30 and Asn-32 residues involved in the major antiparallel β-sheet structure of human epidermal growth factor (hEGF) were substituted with various amino acid residues, and the receptor-binding affinities of the nine variant hEGFs were determined by the use of human KB cells. The Ala-30→Arg. Ala-30→His and Ala-30→Phe substitutions drastically reduced the binding affinity, suggesting that the side chain in position 30 of Ala-30 of hEGF is required to be small for the receptor binding. The Asn-32→Asp substitution significantly reduced the binding affinity, while the Asn-32→His variant could bind to the receptor as well as to the wild-type hEGF. Therefore, it seems to be important for receptor binding that the side chain in position 32 does not have a negative charve but does have an NH group. Thus, we propose that, in the ligand-receptor complex, the receptor recognizes, on one side of the antiparallel β-sheet structure of hEGF, a wider contact area than previously suggested.

Original languageEnglish
Pages (from-to)39-42
Number of pages4
JournalFEBS Letters
Volume302
Issue number1
DOIs
Publication statusPublished - 1992 May 4

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Keywords

  • Epidermal growth factor
  • Protein engineering
  • Site-directed mutagenesis, Human epidermal growth factor receptor

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Koide, H., Muto, Y., Kasai, H., Hoshi, K., Takusari, H., Kohri, K., Takahashi, S., Sasaki, T., Tsukumo, K. I., Miyake, T., Fuwa, T., Miyazawa, T., & Yokoyama, S. (1992). Recognition of an antiparallel β-sheet structure of human epidermal growth factor by its receptor Site-directed mutagenesis studies of Ala-30 and Asn-32. FEBS Letters, 302(1), 39-42. https://doi.org/10.1016/0014-5793(92)80279-P