National Institutes of Health/National Cancer Institute (NIH/NCI)
CA254402
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM117372
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI161880
米国
National Institutes of Health/National Cancer Institute (NIH/NCI)
CA221289
米国
National Institutes of Health/National Cancer Institute (NIH/NCI)
CA023168
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM137505
米国
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)
HL071818
米国
National Institutes of Health/National Cancer Institute (NIH/NCI)
CA023168
米国
Walther Cancer Foundation
米国
Robertson Foundation/Cancer Research Institute
Irvington Postdoctoral Fellowship
米国
VILLUM FONDEN
00025326
デンマーク
Ralph W. and Grace M. Showalter Research Trust
4480108
米国
引用
ジャーナル: Nature / 年: 2025 タイトル: Effect of phosphorylation barcodes on arrestin binding to a chemokine receptor. 著者: Qiuyan Chen / Christopher T Schafer / Somnath Mukherjee / Kai Wang / Martin Gustavsson / James R Fuller / Katelyn Tepper / Thomas D Lamme / Yasmin Aydin / Parth Agrawal / Genki Terashi / Xin- ...著者: Qiuyan Chen / Christopher T Schafer / Somnath Mukherjee / Kai Wang / Martin Gustavsson / James R Fuller / Katelyn Tepper / Thomas D Lamme / Yasmin Aydin / Parth Agrawal / Genki Terashi / Xin-Qiu Yao / Daisuke Kihara / Anthony A Kossiakoff / Tracy M Handel / John J G Tesmer / 要旨: Unique phosphorylation 'barcodes' installed in different regions of an active seven-transmembrane receptor by different G-protein-coupled receptor (GPCR) kinases (GRKs) have been proposed to promote ...Unique phosphorylation 'barcodes' installed in different regions of an active seven-transmembrane receptor by different G-protein-coupled receptor (GPCR) kinases (GRKs) have been proposed to promote distinct cellular outcomes, but it is unclear whether or how arrestins differentially engage these barcodes. Here, to address this, we developed an antigen-binding fragment (Fab7) that recognizes both active arrestin2 (β-arrestin1) and arrestin3 (β-arrestin2) without interacting with bound receptor polypeptides. We used Fab7 to determine the structures of both arrestins in complex with atypical chemokine receptor 3 (ACKR3) phosphorylated in different regions of its C-terminal tail by either GRK2 or GRK5 (ref. ). The GRK2-phosphorylated ACKR3 resulted in more heterogeneous 'tail-mode' assemblies, whereas phosphorylation by GRK5 resulted in more rigid 'ACKR3-adjacent' assemblies. Unexpectedly, the finger loops of both arrestins engaged the micelle surface rather than the receptor intracellular pocket, with arrestin3 being more dynamic, partly because of its lack of a membrane-anchoring motif. Thus, both the region of the barcode and the arrestin isoform involved can alter the structure and dynamics of GPCR-arrestin complexes, providing a possible mechanistic basis for unique downstream cellular effects, such as the efficiency of chemokine scavenging and the robustness of arrestin binding in ACKR3.