Selective effects of charge on G protein activation by FSH-receptor residues 551-555 and 650-653
| Autor: | P, Grasso, M R, Deziel, L E, Reichert |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Male
Sertoli Cells Estradiol Molecular Sequence Data Peptide Fragments Protein Structure Secondary Rats Rats Sprague-Dawley Structure-Activity Relationship GTP-Binding Proteins Electrochemistry Animals Receptors FSH Amino Acid Sequence Guanosine Triphosphate Follicle Stimulating Hormone Cells Cultured |
| Zdroj: | Peptide research. 8(5) |
| ISSN: | 1040-5704 |
| Popis: | Two cytosolic regions of the rat testicular FSH receptor (FSHR), residues 533-555 and 645-653, have been identified as G protein-coupling domains. We localized the activity in these domains to their C-terminal sequences, residues 551-555 (KIAKR, net charge +3) and 650-653 (RKSH, net charge +3), and examined the effects of charge on G protein activation by the C-terminal peptides, using synthetic analogs containing additions, through alanine (A) linkages, of arginine (R, +), histidine (H, +) or both. RA-KIAKR (net charge +4) mimicked the effect of FSHR-(551-555) on guanine nucleotide exchange in rat testis membranes, but reduced its ability to inhibit FSH-stimulated estradiol biosynthesis in cultured rat Sertoli cells. Further increasing net charge by the addition of H (HARA-KIAKR, net charge +5) increased guanosine 5'-triphosphate (GTP) binding, but eliminated FSHR-(551-555) effects on FSH-stimulated steroidogenesis. HA-RKSH (net charge +4) significantly inhibited guanine nucleotide exchange in rat testis membranes, but stimulated basal and potentiated FSH-induced estradiol biosynthesis in cultured rat Sertoli cells. Addition of two H residues (HAHA-RKSH, net charge +5) restored GTP binding and further potentiated basal and FSH-stimulated steroidogenesis. These results suggest that positive charges in G protein-coupling domains of the FSHR play a role in modulating G protein activation and postbinding effects of FSH, such as steroidogenesis. |
| Databáze: | OpenAIRE |
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