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Updated: Sep 12, 2025
12:17
Detection and Isolation of Apoptotic Bodies to High Purity
Published on: August 12, 2018
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Structure and function of the human apoptotic scramblase Xkr4.
Sayan Chakraborty1, Zhang Feng1, Sangyun Lee1
1Department of Anesthesiology, Weill Cornell Medical College, New York, NY, 10027, USA.
Nature Communications
|August 8, 2025
Summary
Human Xkr4 protein scrambles lipids, a key process in cell clearance. This protein thins cell membranes, aiding its function in clearing dying cells and preventing inflammation.
Area of Science:
- Biochemistry
- Cell Biology
- Structural Biology
Background:
- Phosphatidylserine externalization signals dying cells for macrophage clearance.
- X-Kell related (Xkr) proteins mediate this scrambling process.
- Defective Xkr function leads to impaired clearance and inflammation.
Purpose of the Study:
- To investigate the molecular mechanism of human Xkr4 (hXkr4) lipid scrambling.
- To determine the structural basis for hXkr4 scramblase activity.
Main Methods:
- Biochemical purification of full-length monomeric hXkr4.
- Cryo-electron microscopy (CryoEM) for structural determination.
- Molecular dynamics (MD) simulations to analyze membrane interactions.
Main Results:
- Purified monomeric hXkr4 exhibits lipid scrambling activity.
- CryoEM revealed a novel hXkr4 conformation with a negatively charged surface.
- MD simulations demonstrated this conformation thins membranes, correlating with scrambling activity.
Conclusions:
- hXkr4 functions as a monomeric scramblase.
- Membrane thinning induced by hXkr4's unique conformation is crucial for its activity.
- Membrane thinning may be a general mechanism for active lipid scramblases.
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