摘要: Specific arrestin conformations are coupled to distinct downstream effectors, which underlie the functions of many G-protein-coupled receptors (GPCRs). Here, using unnatural amino acid incorporation and fluorine-19 nuclear magnetic resonance (F-19-NMR) spectroscopy, we demonstrate that distinct receptor phospho-barcodes are translated to specific beta-arrestin-1 conformations and direct selective signalling. With its phosphate-binding concave surface, b-arrestin-1 'reads' the message in the receptor phospho-C-tails and distinct phospho-interaction patterns are revealed by F-19-NMR. Whereas all functional phosphopeptides interact with a common phosphate binding site and induce the movements of finger and middle loops, different phospho-interaction patterns induce distinct structural states of b-arrestin-1 that are coupled to distinct arrestin functions. Only clathrin recognizes and stabilizes GRK2-specific b-arrestin-1 conformations. The identified receptor-phosphoselective mechanism for arrestin conformation and the spacing of the multiple phosphatebinding sites in the arrestin enable arrestin to recognize plethora phosphorylation states of numerous GPCRs, contributing to the functional diversity of receptors.
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期刊:
NATURE COMMUNICATIONS
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分类:
生物学
>>
生物物理学
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引用:
ChinaXiv:201605.01441
(或此版本
ChinaXiv:201605.01441V1)
doi:10.12074/201605.01441
CSTR:32003.36.ChinaXiv.201605.01441.V1
- 推荐引用方式:
Yang, Fan,Li, Fa-Hui,Wang, Jiang-Yun,Yang, Fan,Li, Fa-Hui,Wang, Jiang-Yun,Yang, Fan,Yu, Xiao,Liu, Chuan,Qu, Chang-Xiu,Gong, Zheng,Liu, Hong-Da,He, Dong-Fang,Sun, Jin-Peng,Yang, Fan,Yu, Xiao,Liu, Chuan,Qu, Chang-Xiu,Gong, Zheng,Liu, Hong-Da,He, Dong-Fang,Sun, Jin-Peng,Yang, Fan,Yu, Xiao,Wang, Hong-Mei,He, Dong-Fang,Sun, Jin-Peng,Yi, Fan,Song, Chen,Tian, Chang-Lin,Tian, Chang-Lin,Xiao, Kun-Hong,Xiao, Kun-Hong.(2016).Phospho-selective mechanisms of arrestin conformations and functions revealed by unnatural amino acid incorporation and F-19-NMR.NATURE COMMUNICATIONS.[ChinaXiv:201605.01441]
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