The conformational signature of β-arrestin2 predicts its trafficking and signalling functions
| العنوان: | The conformational signature of β-arrestin2 predicts its trafficking and signalling functions |
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| المؤلفون: | Mi-Hye Lee, Louis M. Luttrell, Thomas A. Morinelli, Yuri K. Peterson, Kathryn M. Appleton, Joshua Y. Kwon, Erik G. Strungs, Stéphane A. Laporte |
| المصدر: | Nature. 531:665-668 |
| بيانات النشر: | Springer Science and Business Media LLC, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, education.field_of_study, Multidisciplinary, Beta-Arrestins, media_common.quotation_subject, Population, Biology, Cell biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Heterotrimeric G protein, Arrestin, Arrestin beta 2, Arrestin beta 1, sense organs, education, Internalization, 030217 neurology & neurosurgery, G protein-coupled receptor, media_common |
| الوصف: | Arrestins are cytosolic proteins that regulate G-protein-coupled receptor (GPCR) desensitization, internalization, trafficking and signalling. Arrestin recruitment uncouples GPCRs from heterotrimeric G proteins, and targets the proteins for internalization via clathrin-coated pits. Arrestins also function as ligand-regulated scaffolds that recruit multiple non-G-protein effectors into GPCR-based 'signalsomes'. Although the dominant function(s) of arrestins vary between receptors, the mechanism whereby different GPCRs specify these divergent functions is unclear. Using a panel of intramolecular fluorescein arsenical hairpin (FlAsH) bioluminescence resonance energy transfer (BRET) reporters to monitor conformational changes in β-arrestin2, here we show that GPCRs impose distinctive arrestin 'conformational signatures' that reflect the stability of the receptor-arrestin complex and role of β-arrestin2 in activating or dampening downstream signalling events. The predictive value of these signatures extends to structurally distinct ligands activating the same GPCR, such that the innate properties of the ligand are reflected as changes in β-arrestin2 conformation. Our findings demonstrate that information about ligand-receptor conformation is encoded within the population average β-arrestin2 conformation, and provide insight into how different GPCRs can use a common effector for different purposes. This approach may have application in the characterization and development of functionally selective GPCR ligands and in identifying factors that dictate arrestin conformation and function. |
| تدمد: | 1476-4687 0028-0836 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::35b6d2a7b70195ec6305b91e4f61fd87 https://doi.org/10.1038/nature17154 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........35b6d2a7b70195ec6305b91e4f61fd87 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14764687 00280836 |
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