Post-translational modifications (PTMs) drive the diversity of the proteome and broadly regulate protein function. Interplay between different types of PTMs further enables tight and dynamic fine-tuning of molecular functions. O-Glycosylation on serine, threonine, and tyrosine residues is a major PTM with diverse roles in development, differentiation, pathogenesis, and proteolytic processing. Other examples of cross-talk between PTMs also exist, such as PSGL-1, where the combined presence of N-terminal sulfotyrosines and O-glycans is pivotal for selectin binding. A handful of other related examples of O-glycans and sulfotyrosine co-localization has been described but it is not yet recognized as a general regulatory phenomenon. In this review, we highlight the emerging global pattern of co-localization of cell-surface and extracellular sulfotyrosines with O-glycans, which we term 'multi-motif' interactions, from a wide range of protein classes. We also discuss the barriers, and existing and future tools needed to dissect the biological impact and biomedical potential.

中文翻译：

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酪氨酸硫酸盐和O-糖基化的新兴模式串扰和共定位。

翻译后修饰（PTM）驱动蛋白质组的多样性并广泛调节蛋白质功能。不同类型的PTM之间的相互作用进一步实现了分子功能的紧密和动态微调。丝氨酸，苏氨酸和酪氨酸残基上的O-糖基化是主要的PTM，在发育，分化，发病机理和蛋白水解过程中具有多种作用。还存在PTM之间串扰的其他示例，例如PSGL-1，其中N末端磺基酪氨酸和O-聚糖的组合存在对于选择素结合至关重要。已经描述了O-聚糖和磺基酪氨酸共定位的少数其他相关实例，但是尚未将其视为一般的调节现象。在这篇评论中 我们着重介绍了来自细胞表面和细胞外磺基酪氨酸与O-聚糖共定位的新兴全球模式，我们将其称为“多基元”相互作用，涉及多种蛋白质。我们还讨论了障碍，以及剖析生物影响和生物医学潜力所需的现有和未来工具。