期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms13416
关键词
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资金
- Indian Institute of Technology Kanpur [IITK/BSBE/2014011]
- Department of Science and Technology (DST), Council of Scientific and Industrial Research (CSIR)
- Wellcome Trust/DBT India Alliance
- National Science Foundation of China [21272029]
G Protein-coupled receptors (GPCRs) constitute the largest family of cell surface receptors and drug targets. GPCR signalling and desensitization is critically regulated by beta-arrestins (beta arr). GPCR-beta arr interaction is biphasic where the phosphorylated carboxyl terminus of GPCRs docks to the N-domain of beta arr first and then seven transmembrane core of the receptor engages with barr. It is currently unknown whether fully engaged GPCR-beta arr complex is essential for functional outcomes or partially engaged complex can also be functionally competent. Here we assemble partially and fully engaged complexes of a chimeric beta 2V2R with beta arr1, and discover that the core interaction is dispensable for receptor endocytosis, ERK MAP kinase binding and activation. Furthermore, we observe that carvedilol, a beta arr biased ligand, does not promote detectable engagement between beta arr1 and the receptor core. These findings uncover a previously unknown aspect of GPCR-beta arr interaction and provide novel insights into GPCR signalling and regulatory paradigms.
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