Academic Journal
G protein activation by G protein coupled receptors: ternary complex formation or catalyzed reaction?
| العنوان: | G protein activation by G protein coupled receptors: ternary complex formation or catalyzed reaction? |
|---|---|
| المؤلفون: | Roberts, David J, Waelbroeck, Magali |
| المصدر: | Biochemical pharmacology, 68 (5 |
| سنة النشر: | 2004 |
| المجموعة: | DI-fusion : dépôt institutionnel de l'Université libre de Bruxelles (ULB) |
| مصطلحات موضوعية: | Sciences bio-médicales et agricoles, Animals, Catalysis, GTP-Binding Proteins -- metabolism, Guanosine Diphosphate -- metabolism, Guanosine Triphosphate -- metabolism, Heterotrimeric GTP-Binding Proteins -- metabolism, Humans, Kinetics, Models, Chemical, Protein Conformation, Receptors, G-Protein-Coupled -- metabolism, Signal Transduction -- physiology, agonist, G protein, G protein coupled, G protein coupled receptor, GPCR, Heterotrimeric GTP-binding proteins, Ks, R*activated (as opposed to resting) receptor state, receptor, Signal transduction, Theoretical |
| الوصف: | G protein coupled receptors catalyze the GDP/GTP exchange on G proteins, thereby activating them. The ternary complex model, designed to describe agonist binding in the absence of GTP, is often extended to G protein activation. This is logically unsatisfactory as the ternary complex does not accumulate when G proteins are activated by GTP. Extended models taking into account nucleotide binding exist, but fail to explain catalytic G protein activation. This review puts forward an enzymatic model of G protein activation and compares its predictions with the ternary complex model and with observed receptor phenomenon. This alternative model does not merely provide a new set of formulae but leads to a new philosophical outlook and more readily accommodates experimental observations. The ternary complex model implies that, HRG being responsible for efficient G protein activation, it should be as stable as possible. In contrast, the enzyme model suggests that although a limited stabilization of HRG facilitates GDP release, HRG should not be "too stable" as this might trap the G protein in an inactive state and actually hinder G protein activation. The two models also differ completely in the definition of the receptor "active state": the ternary complex model implies that the active state corresponds to a single active receptor conformation (HRG); in contrast, the catalytic model predicts that the active receptor state is mobile, switching smoothly through various conformations with high and low affinities for agonists (HR, HRG, HRGGDP, HRGGTP, etc.). ; Journal Article ; Research Support, Non-U.S. Gov't ; Review ; info:eu-repo/semantics/published |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 1 full-text file(s): application/pdf |
| اللغة: | English |
| Relation: | uri/info:doi/10.1016/j.bcp.2004.05.044; uri/info:pii/S0006295204003867; uri/info:pmid/15294442; uri/info:scp/4043110585; https://dipot.ulb.ac.be/dspace/bitstream/2013/57518/1/Elsevier_33575.pdf; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/57518 |
| الاتاحة: | http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/57518 https://dipot.ulb.ac.be/dspace/bitstream/2013/57518/1/Elsevier_33575.pdf |
| رقم الانضمام: | edsbas.869E3687 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |