Tyrosine sulfation
In
Function
Sulfation plays a role in strengthening protein-protein interactions. Types of human proteins known to undergo tyrosine sulfation include adhesion molecules, G-protein-coupled receptors, coagulation factors,
By knock-out of TPST genes in mice, it may be observed that tyrosine sulfation has effects on the growth of the mice, such as body weight, fecundity, and postnatal viability.
Mechanism
Sulfation is catalyzed by
Regulation
There is very limited evidence that the TPST genes are subject to transcriptional regulation and tyrosine O-sulfate is very stable and cannot be easily degraded by mammalian sulfatases. Tyrosine O-sulfation is an irreversible process in vivo.
Clinical Significance
It has been shown that the sulfation of Tyr1680 in Factor VIII is essential for effective binding to vWF. Thus, when this is mutated, patients may suffer mild haemophiliac symptoms due to increased turnover.[6] Sulfation of the three tyrosines found in human PSGL-1 not only enhance its binding to P-selectin[7] but also enables its pH-selective binding to the immune checkpoint protein VISTA.[8]
Antibody for detection of tyrosine-sulfated epitopes
In 2006, an article was published in the Journal of Biological Chemistry describing the production and characterization of an antibody called PSG2. This antibody shows exquisite sensitivity and specificity for epitopes containing sulfotyrosine independent of the sequence context.
References
- Moore KL (2003). "The biology and enzymology of protein tyrosine O-sulfation". J. Biol. Chem. 278 (27): 24243–6. PMID 12730193.
- Hoffhines AJ; Damoc, E; Bridges, KG; Leary, JA; Moore, KL (2006). "Detection and purification of tyrosine-sulfated proteins using a novel anti-sulfotyrosine monoclonal antibody". J. Biol. Chem. 281 (49): 37877–87. PMID 17046811.