Structural basis and mechanism of activation of two different families of G proteins by the same GPCR
| Autor: | Joel R. Meyerson, Richard K Hite, Edward T. Eng, Jian-Shu Lou, Jianyun Huang, Kelsey D. Jordan, Xin-Yun Huang, Minfei Su, Kamela O. Alegre, Navid Paknejad |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Gs alpha subunit
Heart Diseases G protein Gi alpha subunit GTP-Binding Protein alpha Subunits Gi-Go Protein Structure Secondary Article Cell Line Structural Biology Cyclic AMP GTP-Binding Protein alpha Subunits Gs Sf9 Cells Animals Humans Cardiac Output Receptor Molecular Biology G protein-coupled receptor Chemistry Mechanism (biology) Cryoelectron Microscopy Isoproterenol Protein Structure Tertiary Enzyme Activation Coupling (electronics) HEK293 Cells Hypertension Biophysics Receptors Adrenergic beta-1 Intracellular Signal Transduction |
| Zdroj: | Nat Struct Mol Biol |
| ISSN: | 1545-9985 1545-9993 |
| Popis: | The β1-adrenergic receptor (β1-AR) can activate two families of G proteins. When coupled to Gs, β1-AR increases cardiac output, and coupling to Gi leads to decreased responsiveness in myocardial infarction. By comparative structural analysis of turkey β1-AR complexed with either Gi or Gs, we investigate how a single G-protein-coupled receptor simultaneously signals through two G proteins. We find that, although the critical receptor-interacting C-terminal α5-helices on Gαi and Gαs interact similarly with β1-AR, the overall interacting modes between β1-AR and G proteins vary substantially. Functional studies reveal the importance of the differing interactions and provide evidence that the activation efficacy of G proteins by β1-AR is determined by the entire three-dimensional interaction surface, including intracellular loops 2 and 4 (ICL2 and ICL4). This study reveals the structural basis for the coupling specificity of one G-protein-coupled receptor, the β1-adrenergic receptor, to two different families of G proteins. Although the receptor adopts the same conformation, the G proteins have different interaction modes dictated by the overall structure. |
| Databáze: | OpenAIRE |
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