Tyrosinesulfated

Tyrosinesulfated refers to a tyrosine residue in a protein that has been modified by the covalent addition of a sulfate group to its phenolic hydroxyl, forming a tyrosine O-sulfate. This post-translational modification is common in secreted and membrane proteins of eukaryotes and is carried out within the secretory pathway.

Biosynthesis and occurrence: The sulfate moiety is donated by 3'-phosphoadenosine-5'-phosphosulfate (PAPS) and transferred by Golgi-localized tyrosylprotein sulfotransferases, primarily TPST-1 and TPST-2. Sulfation occurs on luminal or extracellular regions of proteins as they mature and pass through the secretory pathway, before reaching their final cellular location. The targeting motifs for tyrosine sulfation are variable and not defined by a single strict consensus, but acidic residues near the sulfated tyrosine are a common feature.

Functional significance: Tyrosine sulfation often modulates protein–protein interactions and ligand recognition. It is particularly important for interactions with selectins and chemokine receptors, influencing cell adhesion, immune signaling, and receptor binding. In membrane receptors such as CCR5, sulfated tyrosines in the N-terminus contribute to high-affinity ligand or pathogen protein binding. The modification can affect protein stability, trafficking, and antigenicity, aiding precise extracellular communication.

Detection and scope: Tyrosine sulfation is detected by mass spectrometry and, in some cases, by antibodies specific for sulfotyrosine. It is considered a relatively stable modification, tied to the protein’s maturation in the secretory pathway and dependent on the activity of TPST enzymes. Examples include PSGL-1, CCR5, and various secreted factors and receptors.