1.A.105 The Mixed Lineage Kinase Domain-like (MLKL) Family 

The mixed lineage kinase domain-like (MLKL) protein is a key factor in tumor necrosis factor-induced necroptosis. Studies on necroptosis execution revealed a commitment role of MLKL in membrane disruption. Xia et al. 2016 demonstrated that MLKL forms cation channels that are permeable preferentially to Mg2+ rather than Ca2+ 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, helix H1, H2, H3, H5 and H6 appeared to be transmembrane segments, while H4 is located in the cytoplasm. Finally, MLKL-induced membrane depolarization and cell death exhibit a positive correlation to its channel activity. The Mg2+-preferred permeability and five transmembrane segment topology distinguish MLKL from previously identified Mg2+-permeable channels and thus establish MLKL as a novel class of cation channels.



This family belongs to the Ankyrin Repeat Domain-containing (Ank) Family, found in at least some proteins in the following TC families .

 

References:

Xia, B., S. Fang, X. Chen, H. Hu, P. Chen, H. Wang, and Z. Gao. (2016). MLKL forms cation channels. Cell Res 26: 517-528.

Examples:

TC#NameOrganismal TypeExample
1.A.105.1.1

The mixed lineage kinase domain-like (MLKL) protein of 471 aas and 5 TMSs; forms Mg2+-selective channels in the presence of Na+ and K+ (Xia et al. 2016).

MLKL of Homo sapiens

 
1.A.105.1.2

Mixed lineage kinase domain-like protein, MLKL, of 711 aas and 4 N-terminal TMSs.

MLKL of Balaenoptera acutorostrata scammoni (whale)

 
1.A.105.1.3

Mixed lineage kinase domain-like protein, MLKL, isoform X1 of 503 aas.

MLKL of Acanthaster planci