Proteolysis of Proteins

doi:10.1002/9781119053354.ch15

Cited by 6 publications

(1 citation statement)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rather than resembling a protease's selfcleavage, selenok shares commonalities with self-cleaving peptides in proteins that employ chemical proteolysis, exemplified by the peptide-induced self-cleavage of tyrosinase (Kampatsikas et al, 2019) or the self-cleavage of antibodies' hinge and domain-domain interfaces (Cordoba et al, 2005). Chemical proteolysis is a general term for non-enzymatic cleavage that is mediated by neighboring residues in contact with an exposed protein backbone (Raju, 2019). It is typically driven by b-elimination, such as a nucleophilic attack by an aspartate or isoaspartate residue, the deamidation of glutamine and asparagine residues, or the degradation of disulfide bonds, and can also involve oxidation, isomerization, and light or metal-induced damage (Manning et al, 2010;Reubsaet et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

The Unconventional Self-Cleavage of Selenoprotein K

Cheng¹,

Liu

Mb³

et al. 2021

Preprint

View full text Add to dashboard Cite

Through known association with other proteins, human selenoprotein K (selenok) is currently implicated in the palmitoylation of proteins, degradation of misfolded proteins, innate immune response, and the life cycle of SARS-CoV-2 virus. However, neither the catalytic function of selenok's selenocysteine (Sec), which, curiously, resides in an intrinsically disordered protein segment nor selenok's specific role in these pathways are known to date. This report casts these questions in a new light as it describes that selenok is able -both in vitro and in vivo- to cleave some of its own peptide bonds. The cleavages not only release selenok segments that contain its reactive Sec, but as the specific cleavage sites were identified, they proved to cluster tightly near sites through which selenok interacts with protein partners. Furthermore, it is shown that selenok's cleavage activity is neither restricted to itself nor promiscuous but selectively extends to at least one of its protein partners. Together, selenok's cleavage ability and its features have all hallmarks of a regulatory mechanism that could play a central role in selenok's associations with other proteins and its cellular functions overall.

show abstract