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Updated: Apr 23, 2026
11:55
Membrane Transport Processes Analyzed by a Highly Parallel Nanopore Chip System at Single Protein Resolution
Published on: August 16, 2016
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A plug release mechanism for membrane permeation by MLKL.
Lijing Su1, Bradley Quade1, Huayi Wang2
1Department of Biophysics, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
Structure (London, England : 1993)
|September 16, 2014
Summary
The mixed lineage kinase domain-like (MLKL) protein
Area of Science:
- Molecular Biology
- Cell Death Research
- Structural Biology
Background:
- Mixed lineage kinase domain-like (MLKL) is essential for necroptosis, a programmed cell death pathway.
- MLKL's N-terminal region is responsible for membrane permeabilization, but the exact mechanism remains unclear.
Purpose of the Study:
- To elucidate the structural mechanism by which the MLKL N-terminal region permeabilizes membranes during necroptosis.
Main Methods:
- Nuclear magnetic resonance (NMR) spectroscopy to determine the solution structure of the MLKL N-terminal region.
- Fluorescence spectroscopy to study membrane interactions and liposome leakage assays.
Main Results:
- The MLKL N-terminal region forms a unique six-helix bundle structure.
- The four-helix bundle core inserts into membranes and induces liposome leakage.
- A C-terminal helix (helix 6) acts as an inhibitory plug, preventing bundle opening.
Conclusions:
- The four-helix bundle of MLKL directly mediates membrane breakdown during necroptosis.
- Phosphorylation by RIP3 likely releases the inhibitory C-terminal helix, activating MLKL for membrane permeabilization.
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