Amino acid residue L112 in the ACTH receptor plays a key role in ACTH or α-MSH selectivity
| Autor: | George Ventro, Min Chen, Carroll M. Harmon, Yingkui Yang |
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| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular 0301 basic medicine Agonist endocrine system Protein Conformation medicine.drug_class 030209 endocrinology & metabolism Peptide Adrenocorticotropic hormone Biochemistry 03 medical and health sciences 0302 clinical medicine Endocrinology Adrenocorticotropic Hormone Melanocortin receptor Leucine medicine Humans ACTH receptor Isoleucine Receptor Molecular Biology chemistry.chemical_classification Binding Sites HEK293 Cells 030104 developmental biology Amino Acid Substitution chemistry alpha-MSH Receptor Melanocortin Type 2 hormones hormone substitutes and hormone antagonists |
| Zdroj: | Molecular and Cellular Endocrinology. 482:11-17 |
| ISSN: | 0303-7207 |
| Popis: | The adrenocorticotropic hormone (ACTH) receptor, known as the melanocortin-2 receptor (MC2R), plays a key role in regulating adrenocortical function. MC2R is a subtype of the melanocortin receptor family and ACTH is only agonist for MC2R. Our previous result indicates that ACTH1-17 is the minimal peptide required for MC2R activation but DPhe7-ACTH1-17 has no activity at MC2R. In this study, we examined the molecular basis of the MC2R responsible for ligand selectivity using ACTH analogues and MC2R mutagenesis. Our results indicate that substitution of the 3TM of the MC2R with the corresponding region of the MC3R switches DPhe-ACTH1-17 from no activity to agonist. Further experiment indicates that substitution of the amino acid residue leucine to isoleucine in 112 (L112I) of the 3TM of the MC2R changes both DPhe-ACTH1-17 and ACTH1-15 from no activity to agonists. Surprisingly, mutation L112I switches α-MSH from no activity to agonist, suggesting that this residue plays a key role at MC2R for ligand ACTH or α-MSH selectivity. |
| Databáze: | OpenAIRE |
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