Cell-surface protein thiol (CSPT)

Cell-surface protein thiols (CSTs) are reactive sulfhydryl (-SH) groups located on the extracellular domains of membrane-bound proteins, serving as critical regulators of the exofacial redox environment (PMID: 18251595). These thiols participate in dynamic thiol-disulfide exchange reactions, often catalyzed by enzymes such as protein disulfide isomerase (PDI), which facilitate the conformational changes necessary for cell signaling, adhesion, and the internalization of various ligands (PMID: 22431507). In the context of infectious diseases, CSTs are essential for the entry of several enveloped viruses, including HIV-1 and SARS-CoV-2, by mediating the reduction of viral envelope disulfides to trigger membrane fusion (PMID: 33053377). In oncology, the density and redox state of these thiols are frequently altered to promote tumor cell survival, migration, and resistance to therapy (PMID: 25653188). Therapeutic strategies targeting CSTs involve the use of thiol-reactive small molecules or inhibitors of exofacial thioreductases to block these pathological processes (PMID: 11044601). However, the ubiquitous presence of protein thiols across the human proteome presents a significant challenge for achieving high therapeutic selectivity and minimizing systemic toxicity (PMID: 15128335).

Other names

Exofacial protein thiolCell-surface sulfhydryl groupMembrane protein thiolExofacial thiolCell-surface thiol

Covalent modification, oxidation, or coordination of exofacial sulfhydryl groups to inhibit thiol-disulfide exchange reactions required for protein conformational changes, activation, or viral-host membrane fusion (PMID: 11044601, 33053377).