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Updated: Nov 5, 2025
Study of Protein Dynamics via Neutron Spin Echo Spectroscopy
Published on: April 13, 2022
Conformation of myelin basic protein bound to phosphatidylinositol membrane characterized by vacuum-ultraviolet
Munehiro Kumashiro1, Yudai Izumi2, Koichi Matsuo2
1Department of Physical Science, Graduate School of Science, Hiroshima University, Hiroshima, Japan.
Abstract:
The 18.5-kDa isoform of myelin basic protein (MBP) interacts with the membrane surface of the myelin sheath to construct its compact multilamellar structure. This study characterized the conformation of MBP in the membrane by measuring the vacuum-ultraviolet circular-dichroism (VUVCD) spectra of MBP in the bilayer liposome comprising the following essential lipid constituents of the myelin sheath: phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2). The spectra of MBP exhibited the characteristic peaks of the helix structure in the presence of PI liposome, and the intensity increased markedly in the presence of PIP and PIP2 liposomes to show an isodichroic point. This suggests that the amount of the membrane-bound conformation of MBP enhanced due to the increased number of negative net charges on the liposome surfaces. Secondary-structure analysis revealed that MBP in the membrane comprised approximately 40% helix contents and eight helix segments. Molecular-dynamics (MD) simulations of the eight segments were conducted for 250 ns in the presence of PI membrane, which predicted two amphiphilic and three nonamphiphilic helices as the membrane-interaction sites. Further analysis of the distances of the amino-acid residues in each segment from the phosphate group suggested that the nonamphiphilic helices interact with the membrane surface electrostatically, while the amphiphilic ones invade the inside of the membrane to produce electrostatic and hydrophobic interactions. These results show that MBP can interact with the PI membrane via amphiphilic and nonamphiphilic helices under the control of a delicate balance between electrostatic and hydrophobic interactions.
Insights
Myelin basic protein (MBP) adopts helical structures when interacting with myelin sheath lipids. Increased negative charges on lipids enhance MBP’s membrane-bound conformation, driven by electrostatic and hydrophobic interactions.
Area of Science:
- Biochemistry
- Structural Biology
- Neuroscience
Background:
- Myelin basic protein (MBP) is crucial for the compact multilamellar structure of the myelin sheath.
- Understanding MBP's membrane interaction is key to myelin structure and function.
Purpose of the Study:
- To characterize the conformational changes of MBP upon interaction with key myelin lipids.
- To elucidate the specific lipid-protein interactions governing MBP's membrane association.
Main Methods:
- Vacuum-ultraviolet circular dichroism (VUVCD) spectroscopy to analyze MBP secondary structure.
- Liposome models composed of phosphatidylinositol (PI), PIP, and PIP2.
- Molecular dynamics (MD) simulations of MBP segments interacting with a PI membrane.
Main Results:
- MBP exhibits helical structures in the presence of PI, PIP, and PIP2 liposomes, with increased helical content correlating with higher negative lipid charges.
- Secondary structure analysis indicated MBP adopts ~40% helix content across eight segments.
- MD simulations identified specific amphipathic and non-amphipathic helical segments involved in membrane binding via electrostatic and hydrophobic forces.
Conclusions:
- MBP's interaction with the PI membrane is mediated by distinct helical segments.
- Both electrostatic and hydrophobic interactions, finely balanced, govern MBP's membrane association and structural role in myelin.
