Structural basis and mechanism of activation of two different families of G proteins by the same GPCR Journal Article
| Authors: | Alegre, K. O.; Paknejad, N.; Su, M.; Lou, J. S.; Huang, J.; Jordan, K. D.; Eng, E. T.; Meyerson, J. R.; Hite, R. K.; Huang, X. Y. |
| Article Title: | Structural basis and mechanism of activation of two different families of G proteins by the same GPCR |
| Abstract: | 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). © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc. |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 28 |
| Issue: | 11 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2021-11-01 |
| Start Page: | 936 |
| End Page: | 944 |
| Language: | English |
| DOI: | 10.1038/s41594-021-00679-2 |
| PROVIDER: | scopus |
| PUBMED: | 34759376 |
| PMCID: | PMC8719444 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2021 -- Source: Scopus |
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