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Phospho-selective mechanisms of arrestin... by unnatural amino acid incorporation and 19F-NMR, Nature Communications 6,Published 08 September 2015

发布时间:2015年11月10日

Nature Communications 6, Article number:8202,doi:10.1038/ncomms9202,Published 08 September 2015

Phospho-selective mechanisms of arrestin conformations and functions revealed by unnatural amino acid incorporation and 19F-NMR

Fan Yang, Xiao Yu, Chuan Liu, Chang-Xiu Qu, Zheng Gong, Hong-Da Liu, Fa-Hui Li, Hong-Mei Wang, Dong-Fang He, Fan Yi, Chen Song, Chang-Lin Tian, Kun-Hong Xiao, Jiang-Yun Wang & Jin-Peng Sun

Abstract

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 (19F-NMR) spectroscopy, we demonstrate that distinct receptor phospho-barcodes are translated to specific β-arrestin-1 conformations and direct selective signalling. With its phosphate-binding concave surface, β-arrestin-1 ‘reads’ the message in the receptor phospho-C-tails and distinct phospho-interaction patterns are revealed by 19F-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 β-arrestin-1 that are coupled to distinct arrestin functions. Only clathrin recognizes and stabilizes GRK2-specific β-arrestin-1 conformations. The identified receptor-phospho-selective mechanism for arrestin conformation and the spacing of the multiple phosphate-binding sites in the arrestin enable arrestin to recognize plethora phosphorylation states of numerous GPCRs, contributing to the functional diversity of receptors.

相关报道:http://www.ibp.cas.cn/kyjz/zxdt/201509/t20150909_4422350.html

文章链接:http://www.nature.com/ncomms/2015/150907/ncomms9202/full/ncomms9202.html

 

 

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