Positive Charges in the Brace Region Facilitate the Membrane Disruption of MLKL-NTR in Necroptosis.

ABSTRACT: Necroptosis is a type of programmed cell death executed through the plasma membrane disruption by mixed lineage kinase domain-like protein (MLKL). Previous studies have revealed that an N-terminal four-helix bundle domain (NBD) of MLKL is the executioner domain for the membrane permeabilization, which is auto-inhibited by the first brace helix (H6). After necroptosis initiation, this inhibitory brace helix detaches and the NBD can integrate into the membrane, and hence leads to necroptotic cell death. However, how the NBD is released and induces membrane rupture is poorly understood. Here, we reconstituted MLKL_2-154 into membrane mimetic bicelles and observed the structure disruption and membrane release of the first brace helix that is regulated by negatively charged

SUBMITTER: Yang Y 

PROVIDER: S-EPMC8433767 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature