Perforin proteostasis is regulated through its C2 domain: supra-physiological cell death mediated by T431D-perforin.

ABSTRACT: The pore forming, Ca²⁺-dependent protein, perforin, is essential for the function of cytotoxic lymphocytes, which are at the frontline of immune defence against pathogens and cancer. Perforin is a glycoprotein stored in the secretory granules prior to release into the immune synapse. Congenital perforin deficiency causes fatal immune dysregulation, and is associated with various haematological malignancies. At least 50% of pathological missense mutations in perforin result in protein misfolding and retention in the endoplasmic reticulum. However, the regulation of perforin proteostasis remains unexplored. Using a variety of biochemical assays that assess protein stability and acquisition of complex glycosylation, we demonstrated that the binding of Ca²⁺ to the C2 doma

SUBMITTER: Brennan AJ 

PROVIDER: S-EPMC6113324 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature