MLKL forms cation channels.

ABSTRACT: The mixed lineage kinase domain-like (MLKL) protein is a key factor in tumor necrosis factor-induced necroptosis. Recent studies on necroptosis execution revealed a commitment role of MLKL in membrane disruption. However, our knowledge of how MLKL functions on membrane remains very limited. Here we demonstrate that MLKL forms cation channels that are permeable preferentially to Mg(2+) rather than Ca(2+) in the presence of Na(+) and K(+). Moreover, the N-terminal domain containing six helices (H1-H6) is sufficient to form channels. Using the substituted cysteine accessibility method, we further determine that helix H1, H2, H3, H5 and H6 are transmembrane segments, while H4 is located in the cytoplasm. Finally, MLKL-induced membrane depolarization and cell death exhibit a positive correlatio

SUBMITTER: Xia B 

PROVIDER: S-EPMC4856759 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature