Abstract：
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.
摘要：
β-抑制素的结合和功能受G蛋白偶联受体（GPCRs）中存在的特定磷酸化基序调节。然而,负责建立稳定相互作用的磷酸化氨基酸的确切排列仍不清楚。我们采用在具有已建立的β-抑制蛋白结合特性的GPCR上训练的1D序列卷积模型。通过这种方法，可以鉴定与β-抑制蛋白形成稳定相互作用的GPCRs的氨基酸基序，我们称之为“逮捕”的模式。\"有趣的是,arreSTick模式也存在于许多非受体蛋白中。使用邻近生物素化测定和质谱分析，我们证明arreSTick基序控制许多非受体蛋白和β-arrestin2之间的相互作用。HIV-1Tat特异性因子1（HTSF1或HTATSF1），核转录因子,包含arrestick模式，其亚细胞定位受β-arrestin2的影响。我们的发现揭示了β-抑制素在磷酸化依赖性相互作用中的更广泛作用，延伸到GPCRs之外，也涵盖非受体蛋白。
