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Comprehensive Atlas of the Myelin Basic Protein Interaction Landscape
Evgeniya V Smirnova1, Tatiana V Rakitina1, Rustam H Ziganshin1
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
Biomolecules
|November 27, 2021
Summary
Myelin basic protein (MBP), crucial in multiple sclerosis, interacts with proteins involved in translation and RNA processing. These interactions suggest MBP plays a role in regulating myelination beyond its structural function.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Intrinsically disordered myelin basic protein (MBP) is a key autoantigen in autoimmune neurodegeneration and multiple sclerosis.
- MBP's disordered nature makes its intracellular interactions largely unknown.
Purpose of the Study:
- To identify intracellular proteins interacting with MBP in mammalian cells.
- To elucidate the functional network of MBP.
Main Methods:
- Formaldehyde-induced cross-linking followed by immunoprecipitation.
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Main Results:
- MBP interacts with proteins of the translation machinery and RNA regulation, including ribosomal proteins, Ddx28, STAU1, TDP-43, ADAR-1, and hnRNP A0.
- Identified CTNND1, essential for myelinating Schwann cells, and MAGEB2/D2 proteins linked to neuronal survival/death pathways.
- MBP interacts with RNF40, a component of the E3 ligase complex regulating peripheral myelination.
Conclusions:
- MBP's interactome includes key players in translation, RNA processing, and myelination regulation.
- These findings suggest MBP actively participates in regulating myelination, not just as a structural component.
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