Acylation of MLKL impacts its function in necroptosis.

ABSTRACT: Mixed lineage kinase domain-like (MLKL) is a key signaling protein of necroptosis. Upon activation by phosphorylation, MLKL translocates to the plasma membrane and induces membrane permeabilization which contributes to the necroptosis-associated inflammation. Membrane binding of MLKL is initially initiated by the electrostatic interactions between the protein and membrane phospholipids. We previously showed that MLKL and its phosphorylated form (pMLKL) are S-acylated during necroptosis. Here, we characterize acylation sites of MLKL and identify multiple cysteines that can undergo acylation with an interesting promiscuity at play. Our results show that MLKL and pMLKL undergo acylation at a single cysteine, C184, C269 and C286 are the possible acylation sites. Using all atom molecular

SUBMITTER: Pradhan AJ 

PROVIDER: S-EPMC10462141 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature