tyrosylproteins

Tyrosylproteins are proteins that bear sulfated tyrosine residues, a post-translational modification known as tyrosine sulfation. This modification is installed in the secretory pathway, specifically in the trans-Golgi network, by tyrosylprotein sulfotransferases (TPSTs) using 3'-phosphoadenosine-5'-phosphosulfate (PAPS) as the sulfate donor. In humans, two TPST enzymes, TPST-1 and TPST-2, mediate the reaction, which targets nascent proteins destined for secretion or plasma membrane localization. Sulfation occurs on exposed extracellular tyrosines and tends to influence interactions rather than enzymatic activity.

The functional impact of tyrosyl sulfation is to modulate protein–protein interactions. Sulfated tyrosines often serve as specific binding determinants for binding partners such as selectins, chemokines, and viral envelope proteins. This modification can alter ligand affinity, receptor activation, and cell adhesion, thereby influencing processes like immune cell trafficking, inflammation, and pathogen entry. Notable examples include the N-terminal sulfotyrosines of PSGL-1 that mediate selectin binding, and the sulfated tyrosines at the N-termini of chemokine receptors such as CCR5 and CXCR4, which are important for chemokine recognition and, in the case of CCR5, HIV gp120 attachment.

Tyrosyl sulfation is distinct from tyrosine phosphorylation and is largely irreversible in mature proteins. It is widespread in vertebrates and influences multiple physiological pathways; dysregulation of TPST activity or sulfation patterns is linked to immune and developmental disorders, and TPSTs are explored as potential therapeutic targets.