Identification of a Ligand-Binding Region of the Human Insulin Receptor Encoded by the Second Exon of the Gene
| Autor: | Jia Li Gu, Jonathan Whittaker, Pierre De Meyts, Bruce E. Kaplan, Graeme I. Bell, Ronald M. Shymko |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
endocrine system
Transcription Genetic Phenylalanine medicine.medical_treatment Molecular Sequence Data Mutant Ligands Transfection medicine.disease_cause Exon Endocrinology Mutant protein Complementary DNA Insulin receptor substrate medicine Humans Insulin Amino Acid Sequence Molecular Biology Cells Cultured Mutation biology nutritional and metabolic diseases DNA Exons General Medicine Molecular biology Receptor Insulin Insulin receptor Genes biology.protein hormones hormone substitutes and hormone antagonists |
| Zdroj: | Molecular Endocrinology. 4:409-416 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | Structure-function studies of the insulin molecule indicate that an insulin B chain domain comprising residues 22-26 is involved both in binding to the insulin receptor (INSR) and in insulin dimer formation, suggesting that this domain might also interact with a structure resembling the insulin dimer interface in the INSR. Expression of a mutant INSR cDNA with a deletion of the region corresponding to exon 2 of the INSR gene produces a protein devoid of insulin-binding activity, although the mutant protein is processed appropriately to alpha- and beta-subunits, suggesting that the insulin-binding domain is encoded at least in part by exon 2. Within this region of the INSR molecule, the sequence 83-103 fulfills the structural criteria for a dimer interface. Studies of mutant INSRs with substitutions for phenylalanine 88 or 89 show that the presence of phenylalanine at position 89 is essential for full binding affinity. |
| Databáze: | OpenAIRE |
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