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Recognition of an antiparallel beta-sheet structure of human epidermal growth factor by its receptor. Site-directed mutagenesis studies of Ala-30 and Asn-32. 1992

H Koide, and Y Muto, and H Kasai, and K Hoshi, and H Takusari, and K Kohri, and S Takahashi, and T Sasaki, and K Tsukumo, and T Miyake
Department of Biophysics and Biochemistry, Faculty of Science, University of Tokyo, Japan.

The Ala-30 and Asn-32 residues involved in the major antiparallel beta-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 charge but does have an NH group. Thus, we propose that, in the ligand-receptor complex, the receptor recognizes, on one side of the antiparallel beta-sheet structure of hEGF, a wider contact area than previously suggested.

UI MeSH Term Description Entries
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D004815 Epidermal Growth Factor A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form. EGF,Epidermal Growth Factor-Urogastrone,Urogastrone,Human Urinary Gastric Inhibitor,beta-Urogastrone,Growth Factor, Epidermal,Growth Factor-Urogastrone, Epidermal,beta Urogastrone
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000409 Alanine A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM. Abufène,Alanine, L-Isomer,L-Alanine,Alanine, L Isomer,L Alanine,L-Isomer Alanine
D001216 Asparagine A non-essential amino acid that is involved in the metabolic control of cell functions in nerve and brain tissue. It is biosynthesized from ASPARTIC ACID and AMMONIA by asparagine synthetase. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed) L-Asparagine
D001667 Binding, Competitive The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements. Competitive Binding
D016297 Mutagenesis, Site-Directed Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion. Mutagenesis, Oligonucleotide-Directed,Mutagenesis, Site-Specific,Oligonucleotide-Directed Mutagenesis,Site-Directed Mutagenesis,Site-Specific Mutagenesis,Mutageneses, Oligonucleotide-Directed,Mutageneses, Site-Directed,Mutageneses, Site-Specific,Mutagenesis, Oligonucleotide Directed,Mutagenesis, Site Directed,Mutagenesis, Site Specific,Oligonucleotide Directed Mutagenesis,Oligonucleotide-Directed Mutageneses,Site Directed Mutagenesis,Site Specific Mutagenesis,Site-Directed Mutageneses,Site-Specific Mutageneses
D066246 ErbB Receptors A family of structurally related cell-surface receptors that signal through an intrinsic PROTEIN-TYROSINE KINASE. The receptors are activated upon binding of specific ligands which include EPIDERMAL GROWTH FACTORS, and NEUREGULINS. EGF Receptor,Epidermal Growth Factor Receptor,Epidermal Growth Factor Receptor Family Protein,Epidermal Growth Factor Receptor Protein-Tyrosine Kinase,ErbB Receptor,HER Family Receptor,Receptor, EGF,Receptor, Epidermal Growth Factor,Receptor, TGF-alpha,Receptor, Transforming-Growth Factor alpha,Receptor, Urogastrone,Receptors, Epidermal Growth Factor-Urogastrone,TGF-alpha Receptor,Transforming Growth Factor alpha Receptor,Urogastrone Receptor,c-erbB-1 Protein,erbB-1 Proto-Oncogene Protein,EGF Receptors,Epidermal Growth Factor Receptor Family Proteins,Epidermal Growth Factor Receptor Kinase,HER Family Receptors,Proto-oncogene c-ErbB-1 Protein,Receptor Tyrosine-protein Kinase erbB-1,Receptor, ErbB-1,Receptors, Epidermal Growth Factor,Epidermal Growth Factor Receptor Protein Tyrosine Kinase,ErbB-1 Receptor,Family Receptor, HER,Family Receptors, HER,Proto oncogene c ErbB 1 Protein,Proto-Oncogene Protein, erbB-1,Receptor Tyrosine protein Kinase erbB 1,Receptor, ErbB,Receptor, ErbB 1,Receptor, HER Family,Receptor, TGF alpha,Receptor, Transforming Growth Factor alpha,Receptors, EGF,Receptors, Epidermal Growth Factor Urogastrone,Receptors, ErbB,Receptors, HER Family,c erbB 1 Protein,c-ErbB-1 Protein, Proto-oncogene,erbB 1 Proto Oncogene Protein

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