| Autor: |
He, Qing-Tao, Xiao, Peng, Huang, Shen-Ming, Jia, Ying-Li, Zhu, Zhong-Liang, Lin, Jing-Yu, Yang, Fan, Tao, Xiao-Na, Zhao, Ru-Jia, Gao, Feng-Yuan, Niu, Xiao-Gang, Xiao, Kun-Hong, Wang, Jiangyun, Jin, Changwen, Sun, Jin-Peng, Yu, Xiao |
| Předmět: |
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| Zdroj: |
Nature Communications; 4/22/2021, Vol. 12 Issue 1, p1-16, 16p |
| Abstrakt: |
Arrestins recognize different receptor phosphorylation patterns and convert this information to selective arrestin functions to expand the functional diversity of the G protein-coupled receptor (GPCR) superfamilies. However, the principles governing arrestin-phospho-receptor interactions, as well as the contribution of each single phospho-interaction to selective arrestin structural and functional states, are undefined. Here, we determined the crystal structures of arrestin2 in complex with four different phosphopeptides derived from the vasopressin receptor-2 (V2R) C-tail. A comparison of these four crystal structures with previously solved Arrestin2 structures demonstrated that a single phospho-interaction change results in measurable conformational changes at remote sites in the complex. This conformational bias introduced by specific phosphorylation patterns was further inspected by FRET and 1H NMR spectrum analysis facilitated via genetic code expansion. Moreover, an interdependent phospho-binding mechanism of phospho-receptor-arrestin interactions between different phospho-interaction sites was unexpectedly revealed. Taken together, our results provide evidence showing that phospho-interaction changes at different arrestin sites can elicit changes in affinity and structural states at remote sites, which correlate with selective arrestin functions. The interaction between a GPCR, such as the vasopressin receptor-2 (V2R), and arrestin depends on the receptors' phosphorylation pattern. Here authors use FRET and NMR to analyze the phosphorylation patterns of the V2R-arrestin complex and show that phospho-interactions are the key determinants of selective arrestin conformational states and correlated functions. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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