دورية أكاديمية
Mutations at the domain interface of GSalpha impair receptor-mediated activation by altering receptor and guanine nucleotide binding.
| العنوان: | Mutations at the domain interface of GSalpha impair receptor-mediated activation by altering receptor and guanine nucleotide binding. |
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| المؤلفون: | Grishina G; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8026, USA., Berlot CH |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 1998 Jun 12; Vol. 273 (24), pp. 15053-60. |
| نوع المنشور: | Journal Article; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print Cited Medium: Print ISSN: 0021-9258 (Print) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | GTP-Binding Proteins/*chemistry, Adenylyl Cyclases/metabolism ; Aluminum Compounds/pharmacology ; Binding, Competitive/physiology ; Enzyme Activation/drug effects ; Fluorides/pharmacology ; GTP Phosphohydrolases/chemistry ; GTP-Binding Proteins/genetics ; Guanosine Triphosphate/analogs & derivatives ; Guanosine Triphosphate/metabolism ; Iodocyanopindolol ; Isoproterenol/metabolism ; Models, Molecular ; Mutation/genetics ; Pindolol/analogs & derivatives ; Pindolol/metabolism ; Protein Binding ; Protein Structure, Secondary ; Receptors, Adrenergic, beta/physiology ; Transfection/genetics ; Tumor Cells, Cultured |
| مستخلص: | G protein alpha subunits consist of two domains, a GTPase domain and a helical domain. Receptors activate G proteins by catalyzing replacement of GDP, which is buried between these two domains, with GTP. Substitution of the homologous alphai2 residues for four alphas residues in switch III, a region that changes conformation upon GTP binding, or of one nearby helical domain residue decreases the ability of alphas to be activated by the beta-adrenergic receptor and by aluminum fluoride. Both sets of mutations increase the affinity of alphas for the beta-adrenergic receptor, based on an increased amount of high affinity binding of the beta-adrenergic agonist, isoproterenol. The mutations also decrease the rate of receptor-mediated activation and disrupt the ability of the beta-adrenergic receptor to increase the apparent affinity of alphas for the GTP analog, guanosine 5'-O-(3-thiotriphosphate). Simultaneous replacement of the helical domain residue and one of the four switch III residues with the homologous alphai2 residues restores normal receptor-mediated activation, suggesting that the defects caused by mutations at the domain interface are due to altered interdomain interactions. These results suggest that interactions between residues across the domain interface are involved in two key steps of receptor-mediated activation, promotion of GTP binding and subsequent receptor-G protein dissociation. |
| معلومات مُعتمدة: | GM50369 United States GM NIGMS NIH HHS |
| المشرفين على المادة: | 0 (Aluminum Compounds) 0 (Receptors, Adrenergic, beta) 83498-72-0 (Iodocyanopindolol) 86-01-1 (Guanosine Triphosphate) BJ4HF6IU1D (Pindolol) EC 3.6.1.- (GTP Phosphohydrolases) EC 3.6.1.- (GTP-Binding Proteins) EC 4.6.1.1 (Adenylyl Cyclases) L628TT009W (Isoproterenol) Q80VPU408O (Fluorides) Z77H3IKW94 (aluminum fluoride) |
| تواريخ الأحداث: | Date Created: 19980617 Date Completed: 19980713 Latest Revision: 20210209 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1074/jbc.273.24.15053 |
| PMID: | 9614114 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0021-9258 |
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| DOI: | 10.1074/jbc.273.24.15053 |