Mass spectrometry (MS)-based proteomics and the sulfome: clinical potential

Daly, Sally, Daly, Leonard, Mesdaghi, Shahram, Jones, Sarah, Rigden, Daniel, Eyers, Patrick and Eyers, Claire ORCID: 0000-0002-3223-5926 (2025) Mass spectrometry (MS)-based proteomics and the sulfome: clinical potential. [Preprint]

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Abstract

Introduction Protein tyrosine sulfation is of growing scientific interest due to its biological and clinical significance, yet it remains an underexplored post-translational modification (PTM). Catalysed by Golgi-localised TPST1 and TPST2, tyrosine sulfation modulates protein–protein interactions and receptor–ligand binding in inflammation, haemostasis, immunity, and viral entry. Despite functional relevance, this modification is underrepresented in databases, in large part due to a lack of robust analytical strategies. Advances in mass spectrometry (MS)-based analyses have recently improved sensitivity of detection, expanding the known tyrosine ‘sulfome’. Systematic profiling of sulfated residues can now be undertaken, expanding knowledge of their regulatory roles in both health and disease, and for pioneering new sulfation-targeted therapeutics. Areas covered We review known biological roles of protein sulfation by TPSTs and approaches for characterisation of sulfotyrosine and other residues such as cysteine. More broadly, we consider how these strategies might be useful in a clinical context. Expert opinion High throughput MS-based proteomics has proven invaluable for the discovery of PTMs, advancing understanding of their roles in human health and disease. With recent advances in strategies for the characterisation of protein sulfation, the field is now ready for exploration in a clinical context.

Item Type:	Preprint
Uncontrolled Keywords:	mass spectrometry, sulfation, post-translational modification, TPST, sulfotyrosine, sulfocysteine
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	16 Sep 2025 07:13
Last Modified:	16 Sep 2025 07:13
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3194422