MBP

What is MBP protein?

MBP gene (myelin basic protein) is a protein coding gene which situated on the long arm of chromosome 18 at locus 18q23. The protein encoded by the classic MBP gene is a major constituent of the myelin sheath of oligodendrocytes and Schwann cells in the nervous system. However, MBP-related transcripts are also present in the bone marrow and the immune system. MBP is the second most abundant protein in the myelin sheath of the central nervous system and is mainly responsible for maintaining the adhesion of the cytoplasmic surface of the multiple layers of tight myelin sheath. MBP is also a 42kDa protein that exists in the periplasmic space of bacteria and is involved in the transport of maltose and maltodextrin across bacterial cell membranes. The MBP protein is consisted of 304 amino acids and MBP molecular weight is approximately 33.1 kDa.

What is the function of MBP protein?

MBP belongs to a family of "intrinsically disordered" or conformationally adaptable proteins that have a variety of other functions in addition to their role in myelination. For example, it can interact with a variety of polyanionic proteins (such as actin, tubulin, Ca^2+^ -calmodulin, and clathrin) as well as negatively charged lipids, and gain structure when it binds to them. In addition, some large and small subtypes of MBP can be transported into the nucleus, so they may also bind to polynucleotides. It may act as a membrane actin-binding protein, potentially participating in the transmission of extracellular signals to the cytoskeleton in oligodendrocytes and tight junctions in myelin. In addition to its structural role, MBP has been implicated in various biological processes, including host defense against parasitic infections, activation of immune cells like mast cells, basophils, and neutrophils, complement activation, platelet agonist activity, antibacterial activity, and acting as a natural protein inhibitor of heparinase.

Fig1. MBP/acetylcholine receptor homology model of pain (a hypothesis diagram). (Veronica I Shubayev, 2018)

MBP Related Signaling Pathway

In terms of signal transduction, MBP itself is not directly involved in the signal transduction pathway, but it is associated with a variety of signal pathways. For example, MBP is closely associated with oligodendrocyte maturation and myelination, and these processes are regulated by multiple cell signaling pathways. In addition, the expression and function of MBP may be influenced by signaling pathways such as TGF-β/ activin and BMP, which signal through members of the Smad protein family to influence cell proliferation, differentiation, and cell fate determination.

BMP signaling relies on heterotetramer serine/threonine kinase receptors, including BMPRI (BMP receptor type I) and BMPRII (BMP receptor type II). BMP binding to its receptor complex leads to activation of BMPRI, which phosphorylates Smad1, Smad5, and Smad8 molecules. These phosphorylated Smad molecules then form complexes with co-SMAD, or Smad4, that migrate into the nucleus to activate transcription of specific genes.

Fig1. Proposed scheme for insulin-stimulated signaling of the proliferation and the production of myelin-related proteins. (Tomokazu Saiki, 2021)

MBP Related Diseases

Because MBP is a key component of the myelin sheath of the central nervous system, abnormalities in it are often associated with diseases that affect nerve conduction. MBP is a major component of the myelin sheath, and its destruction leads to the obstruction of nerve signaling, resulting in Multiple Sclerosis (MS). Other demyelinating diseases include, but are not limited to, inherited metabolic disorders such as adrenoleukodystrophy and Krabbe disease, which can also cause damage to the myelin sheath. The abnormality of MBP may affect the repair process after nerve injury. In addition, meningitis or encephalitis caused by certain viruses and bacteria may cause neurological impairment by affecting the structure of the MBP and myelin sheath.

Bioapplications of MBP

MBP is also widely used as a fusion tag in protein expression and purification. It not only increases the solubility of the target protein, but also provides one-step purification through affinity with the cross-linked starch resin. In addition, when expressed in mammalian cells, the fusion protein of the MBP label is generally able to enhance protein production and reduce the number of cell deaths. Studies have shown that MBP fusion proteins, when expressed in eukaryotic cells, usually exist as monomers and do not cause N-glycosylation, but may cause O-glycosylation. In terms of disease treatment, MBP can be used as a biomarker for monitoring central nervous system damage and demyelinating diseases, and changes in its levels in the cerebrospinal fluid or blood may indicate disease activity and severity. The structural and functional properties of MBP make it a target for drug screening, especially in the search for drugs that can promote myelin regeneration or inhibit inflammation.