MLKL Antibodies

Structure of MLKL

MLKL is a protein kinase-like domain protein with crucial functions. Its molecular weight varies depending on the subtype and post-translational modification status, and is approximately 54-55 kDa in general. This molecular weight shows some differences among different species, as shown in the following table:

The full-length of the MLKL protein typically consists of approximately 470 amino acids, and its three-dimensional structure presents a unique dimeric configuration. The core of this structure lies in its C-terminal pseudokinase domain, which does not have catalytic activity but is responsible for receiving upstream signals; while the N-terminal forms a four-helix bundle execution domain. After the activation of the cell programmed necrosis signaling pathway, specific phosphorylation events will induce conformational changes in MLKL, exposing its N-terminal domain. Subsequently, MLKL undergoes oligomerization and is transported to the cell membrane, where it executes the final cell lysis function by directly disrupting membrane integrity or forming channels. This process is a crucial irreversible step in programmed necrosis.

Fig. 1 Structure and function of MLKL.¹

Key structural properties of MLKL:

• Junctional kinase domain
• Four-helix beam execution domain
• Hinge region connection domain

Functions of MLKL

The main function of the MLKL gene is to mediate programmed cell necrosis. However, it is also involved in the regulation of various other pathological and physiological processes in the body.

Unlike the "silent" clearance of apoptosis, the programmed necrosis mediated by MLKL has obvious pro-inflammatory properties. Its activation process involves a strict multi-level regulation from self-inhibition to oligomerization, which determines its dual roles in physiological and pathological conditions.

Applications of MLKL and MLKL Antibody in Literature

1. Martinez-Osorio, Veronica, Yasmin Abdelwahab, and Uris Ros. "The many faces of MLKL, the executor of necroptosis." International Journal of Molecular Sciences 24.12 (2023): 10108. https://doi.org/10.3390/ijms241210108

The article indicates that the key mechanism by which MLKL mediates membrane rupture during necroptosis remains unclear. This paper reviews its activation pathways, structural functions and disease effects, and summarizes the research progress of related inhibitors.

2. Liu, Shuzhen, et al. "MLKL polymerization-induced lysosomal membrane permeabilization promotes necroptosis." Cell Death & Differentiation 31.1 (2024): 40-52. https://doi.org/10.1038/s41418-023-01237-7

The research found that MLKL forms polymers during necroptosis and transfers to the lysosomal membrane, causing the lysosomal membrane to become permeable, and promoting the release of cathepsin B into the cytoplasm, thereby executing cell death. This reveals a new mechanism by which MLKL polymerization induces lysosomal damage.

3. Geng, Lu, et al. "MLKL deficiency alleviates neuroinflammation and motor deficits in the α-synuclein transgenic mouse model of Parkinson's disease." Molecular Neurodegeneration 18.1 (2023): 94. https://doi.org/10.1186/s13024-023-00686-5

This study reveals that inhibiting or knocking out the key protein MLKL involved in necroptosis can significantly improve the motor symptoms of the Parkinson's disease model, reduce the deposition of α-synuclein and the loss of dopaminergic neurons, and inhibit neuroinflammation, indicating that MLKL is a potential therapeutic target for Parkinson's disease.

4. Zhan, Chaoning, et al. "MLKL: Functions beyond serving as the Executioner of Necroptosis." Theranostics 11.10 (2021): 4759. https://doi.org/10.7150/thno.54072

In addition to mediating necroptosis, the non-apoptotic functions of MLKL have gained increasing attention and are involved in the regulation of various diseases. This article reviews its structure, signaling pathways, and associations with other forms of cell death, with a focus on its new functions and inhibitor progress, providing a reference for clinical targeted therapy.

5. Liccardi, Gianmaria, and Alessandro Annibaldi. "MLKL post-translational modifications: road signs to infection, inflammation and unknown destinations." Cell Death & Differentiation 30.2 (2023): 269-278. https://doi.org/10.1038/s41418-022-01061-5

The article indicates that MLKL is the execution protein for necroptosis, and the activation mechanism of it remains unclear. Besides the known phosphorylation pathway of RIPK3, new post-translational modifications (such as ubiquitination) and the differences between human and mouse MLKL suggest that there are more complex regulatory mechanisms and potential non-apoptotic inflammatory functions of it.

Creative Biolabs: MLKL Antibodies for Research

Creative Biolabs specializes in the production of high-quality MLKL antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom MLKL Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our MLKL antibodies, custom preparations, or technical support, contact us at email.