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Fragmentation of phospholipid bilayers by myelin basic protein
1Department of Physics, University of British Columbia, Vancouver, Canada.
Abstract:
Human myelin basic protein (MBP) is shown to disrupt multilamellar phosphatidylcholine bilayers into small lipoprotein particles in a manner similar to the cytolytic peptide melittin (Dufourc, E. J., Smith, I. C. P., & Dufourcq, J. (1986) Biochemistry 25, 6448-6455). This bilayer fragmentation, as monitored by 31P nuclear magnetic resonance, is temperature-dependent and completely inhibited by the presence of small amounts of negatively charged phosphatidylserine. The stabilizing property of phosphatidylserine is lost with the neutralization of its negative charges upon membrane binding of cationic species such as calcium ions. No MBP-induced fragmentation is observed with bilayers of negative or zwitterionic lipid mixtures which mimic the myelin lipid composition. The membrane fragmentation observed in vitro in the presence of MBP could play a role in vivo in demyelinating diseases.
Insights
Human myelin basic protein (MBP) fragments lipid bilayers, similar to melittin. Negatively charged phosphatidylserine prevents this, but calcium ions abolish its effect, suggesting a role in demyelinating diseases.
Area of Science:
- Biochemistry
- Biophysics
- Neuroscience
Background:
- Myelin basic protein (MBP) is a key component of the myelin sheath.
- Lipid bilayers form the structural basis of cell membranes.
- Demyelinating diseases involve damage to the myelin sheath.
Purpose of the Study:
- To investigate the effect of human myelin basic protein (MBP) on phosphatidylcholine bilayers.
- To elucidate the mechanism of MBP-induced membrane disruption.
- To explore the potential role of MBP in demyelinating diseases.
Main Methods:
- Multilamellar phosphatidylcholine bilayers were used as a model system.
- 31P nuclear magnetic resonance (NMR) spectroscopy monitored bilayer fragmentation.
- Lipid composition, including phosphatidylserine and calcium ions, was varied.
Main Results:
- MBP disrupted phosphatidylcholine bilayers into lipoprotein particles, similar to melittin.
- Bilayer fragmentation was temperature-dependent.
- Negatively charged phosphatidylserine inhibited fragmentation, an effect lost upon calcium ion binding.
- MBP did not fragment bilayers mimicking myelin lipid composition.
Conclusions:
- MBP can induce bilayer fragmentation in vitro.
- Phosphatidylserine stabilizes membranes against MBP-induced disruption.
- Calcium ions neutralize the stabilizing effect of phosphatidylserine.
- MBP-induced membrane fragmentation may contribute to the pathogenesis of demyelinating diseases.