Myelin basic protein

MBP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1ZGL, 1BX2, 1FV1, 1HQR, 1K2D, 1YMM
Identifiers
Aliases	MBP, entrez:4155, myelin basic protein, Myelin basic protein, Myelin_BP, IPR000548
External IDs	OMIM: 159430 MGI: 96925 HomoloGene: 1788 GeneCards: MBP
Gene location (Human) Chr. Chromosome 18 (human)[1] Band 18q23 Start 76,978,827 bp[1] End 77,133,683 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18 E3|18 55.84 cM Start 82,475,146 bp[2] End 82,585,637 bp[2]
RNA expression pattern Bgee Top expressed in brain occipital lobe inferior olivary nucleus substantia nigra subthalamic nucleus inferior ganglion of vagus nerve pons globus pallidus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function GO:0001948 protein binding protease binding calmodulin binding structural constituent of myelin sheath Cellular component nucleus cell projection membrane plasma membrane intracellular anatomical structure internode region of axon neuronal cell body myelin sheath compact myelin cell periphery cell surface protein-containing complex Biological process chemical synaptic transmission membrane organization central nervous system development axon ensheathment substantia nigra development response to toxic substance immune response sensory perception of sound MAPK cascade negative regulation of heterotypic cell-cell adhesion maintenance of blood-brain barrier myelination positive regulation of metalloendopeptidase activity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4155	17196
Ensembl	ENSG00000197971	ENSMUSG00000041607
UniProt	P02686	P04370
RefSeq (mRNA)	NM_001025081 NM_001025090 NM_001025092 NM_001025094 NM_001025098 NM_001025100 NM_001025101 NM_002385	NM_001025245 NM_001025251 NM_001025254 NM_001025255 NM_001025256 NM_001025258 NM_001025259 NM_010777
RefSeq (protein)	NP_001020252 NP_001020261 NP_001020263 NP_001020271 NP_001020272 NP_002376	NP_001020416 NP_001020422 NP_001020425 NP_001020426 NP_001020427 NP_001020429 NP_001020430 NP_034907
Location (UCSC)	Chr 18: 76.98 – 77.13 Mb	Chr 18: 82.48 – 82.59 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Myelin basic protein (MBP) is a protein believed to be important in the process of myelination of nerves in the nervous system. The myelin sheath is a multi-layered membrane, unique to the nervous system, that functions as an insulator to greatly increase the velocity of axonal impulse conduction.^[5] MBP maintains the correct structure of myelin, interacting with the lipids in the myelin membrane.^[6][7]

MBP was initially sequenced in 1971 after isolation from bovine myelin membranes.^[8] MBP knockout mice called shiverer mice were subsequently developed and characterized in the early 1980s. Shiverer mice exhibit decreased amounts of CNS myelination and a progressive disorder characterized by tremors, seizures, and early death. The human gene for MBP is on chromosome 18;^[9] the protein localizes to the CNS and to various cells of the hematopoietic lineage.

The pool of MBP in the central nervous system is very diverse, with several splice variants being expressed and a large number of post-translational modifications on the protein, which include phosphorylation, methylation, deamidation, and citrullination. These forms differ by the presence or the absence of short (10 to 20 residues) peptides in various internal locations in the sequence. In general, the major form of MBP is a protein of about 18.5 Kd (170 residues).

In melanocytic cell types, MBP gene expression may be regulated by MITF.^[10]

Gene expression[]

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. These mRNAs arise from the long MBP gene (otherwise called "Golli-MBP") that contains 3 additional exons located upstream of the classic MBP exons. Alternative splicing from the Golli and the MBP transcription start sites gives rise to 2 sets of MBP-related transcripts and gene products. The Golli mRNAs contain 3 exons unique to Golli-MBP, spliced in-frame to 1 or more MBP exons. They encode hybrid proteins that have N-terminal Golli aa sequence linked to MBP aa sequence. The second family of transcripts contain only MBP exons and produce the well-characterized myelin basic proteins. This complex gene structure is conserved among species, suggesting that the MBP transcription unit is an integral part of the Golli transcription unit and that this arrangement is important for the function and/or regulation of these genes.^[11]

Structure[]

MBP Charge and Citrullination

Myelin basic protein has been classified as an intrinsically disordered protein that has no stable secondary structure in solution.^[12] Like most IDPs, it has a high net charge and a low mean hydrophobicity, minimizing the hydrophobic effect that drives traditional protein folding. It does contain some exceptions to normal IDP amino acid content. For example, MBP has more arginine and less glutamic acid than most IDPs. However, this is likely because those changes are necessary for MBP to be sufficiently basic and positively charged to correctly interact with the membrane.^[13] Notably, MBP has been shown to adopt a more stable secondary structure on interaction with lipids.^[14][15] NMR and Cys-specific spin labeling experiments have predicted this structure to contain beta sheet and regions of amphipathic helix.^[16]

As implied by its name, myelin basic protein is significantly basic, with an isoelectric point of 10. It is thought to associate with the cell membrane through electrostatic interactions between its positive charges and negatively charged phospholipid heads of the plasma membrane.^[17] It can undergo a large variety of post-translational modifications, creating various charge isomers known as C1-C6 or C8.^[18] These modifications include phosphorylation, methylation, deamidation, citrullination, ADP-ribosylation, and N-terminal acylation . C1 is the least modified, while C8 is the most distinct, containing 6-11 additional citrullinations. Since each of these decreases its positive charge, C8 has the smallest net positive charge of the isomers. Alternations in these post-translational modifications have been associated with demyelinating diseases. Notably, MBP isolated from individuals with multiple sclerosis have had a higher degree of citrullination and a smaller positive charge. In a rare, severe form of MS known as Marburg's syndrome, the citrullination was even more extensive.^[17]

Role in disease[]

Interest in MBP has centered on its role in demyelinating diseases, in particular, multiple sclerosis (MS). The target antigen of the autoimmune response in MS has not yet been identified. However, several studies have shown a role for antibodies against MBP in the pathogenesis of MS.^[19] Some studies have linked a genetic predisposition to MS to the MBP gene, though a majority have not.

A "molecular mimicry" hypothesis of multiple sclerosis has been suggested, in which T cells are, in essence, confusing MBP with human herpesvirus-6. Researchers in the United States created a synthetic peptide with a sequence identical to that of an HHV-6 peptide. Elevated levels of MBP have been found in the cerebrospinal fluid of patients with HIV infections and signs of encephalopathy, and although MBP does not seem to be a sensitive diagnostic marker of HIV encephalopathy, it has been suggested that it may serve a role as a prognostic indicator of disease progression.^[20] It is able to show that T cells were activated by this peptide. These activated T cells also recognized and initiated an immune response against a synthetically created peptide sequence that is identical to part of human MBP. During their research, they found that the levels of these cross-reactive T cells are significantly elevated in multiple sclerosis patients.^[21]

Some research has shown that inoculating an animal with MBP to generate an MBP-specific immune response against it increases blood–brain barrier permeability. Permeability is enhanced when the animal is inoculated against non-specific proteins.^[22]

A targeted immune response to MBP has been implicated in lethal rabies infection. The inoculation of MBP generates increases the permeability of the blood–brain barrier (BBB), allowing immune cells to enter the brain, the primary site of rabies virus replication. In a study of mice infected with Silver-haired bat rabies virus (SHBRV), the mortality rate of mice treated with MBP improved 20%-30% over the untreated control group. It is significant to note that healthy uninfected mice treated with MBP showed an increase in mortality rate between 0% and 40%.^[23]

Interactions[]

Myelin basic protein has been shown to interact in vivo with proteolipid protein 1,^[24][25] and in vitro with calmodulin, actin, tropomyosin, tubulin, clathrin, 2',3'-cyclic-nucleotide 3'-phosphodiesterase and multiple molecules of the immune system.^[26]

References[]

Further reading[]

External links[]

• Media related to Myelin basic proteins at Wikimedia Commons
• Overview of all the structural information available in the PDB for UniProt: P02686 (Myelin basic protein) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.