%0 Journal Article
%T ArreSTick motif controls β-arrestin-binding stability and extends phosphorylation-dependent β-arrestin interactions to non-receptor proteins.
%A Tóth AD
%A Soltész-Katona E
%A Kis K
%A Guti V
%A Gilzer S
%A Prokop S
%A Boros R
%A Misák Á
%A Balla A
%A Várnai P
%A Turiák L
%A Ács A
%A Drahos L
%A Inoue A
%A Hunyady L
%A Turu G
%J Cell Rep
%V 43
%N 5
%D 2024 May 28
%M 38758647
暂无%R 10.1016/j.celrep.2024.114241
%X The binding and function of β-arrestins are regulated by specific phosphorylation motifs present in G protein-coupled receptors (GPCRs). However, the exact arrangement of phosphorylated amino acids responsible for establishing a stable interaction remains unclear. We employ a 1D sequence convolution model trained on GPCRs with established β-arrestin-binding properties. With this approach, amino acid motifs characteristic of GPCRs that form stable interactions with β-arrestins can be identified, a pattern that we name "arreSTick." Intriguingly, the arreSTick pattern is also present in numerous non-receptor proteins. Using proximity biotinylation assay and mass spectrometry analysis, we demonstrate that the arreSTick motif controls the interaction between many non-receptor proteins and β-arrestin2. The HIV-1 Tat-specific factor 1 (HTSF1 or HTATSF1), a nuclear transcription factor, contains the arreSTick pattern, and its subcellular localization is influenced by β-arrestin2. Our findings unveil a broader role for β-arrestins in phosphorylation-dependent interactions, extending beyond GPCRs to encompass non-receptor proteins as well.