What is MLKL Protein ?
Mixed lineage kinase domain-like (MLKL) protein is classified as a pseudokinase. It is because the protein contains a kinase-like domain which lacks two of the three conserved residues. The conserved catalytic residues were considered crucial for phosphoryl transfer activity in previous study (Manning et al., 2002).
Pseudokinases have several characteristics which are :
Pseuokinases comprise of roughly 10% of mammalian kinomes and play an important role in cell signalling acting as regulators. Also, they are predominant modulators of bona fide protein kinases. (Zeqiraj and van Aalten, 2010)
Previous research shows that MLKL involves in necroptosis, acting as an interacting target of the RIP kinases RIPK1 and RIPK3 which are essential in the TNF-induced necroptosis process. (Sun et al., 2012 and Wang et al., 2012). However, the role and mechanisms of MLKL remained unclear before James M. Murphy and his team publishing their work.
Pseudokinases have several characteristics which are :
- Reply on Lys of the Val-Ala-Ile-Lys motif for interaction with the α and β phosphates of ATP during phosphotransfer.
- The Asp of the His-Arg-Asp motif acts as a catalytic residue.
- The Asp of the Asp-Phe-Gly motif in the activation loop bind Mg2+ to coordinate the β and γ phosphates of ATP.
Pseuokinases comprise of roughly 10% of mammalian kinomes and play an important role in cell signalling acting as regulators. Also, they are predominant modulators of bona fide protein kinases. (Zeqiraj and van Aalten, 2010)
Previous research shows that MLKL involves in necroptosis, acting as an interacting target of the RIP kinases RIPK1 and RIPK3 which are essential in the TNF-induced necroptosis process. (Sun et al., 2012 and Wang et al., 2012). However, the role and mechanisms of MLKL remained unclear before James M. Murphy and his team publishing their work.