Myelin basic protein

1ZGL, 1BX2, 1FV1, 1HQR, 1K2D, 1YMM415517196ENSG00000197971ENSMUSG00000041607P02686P04370NM_001025100NM_001025101NM_002385NM_001025258NM_001025259NM_010777NP_002376NP_001020429NP_001020430NP_034907Myelin 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. MBP maintains the correct structure of myelin, interacting with the lipids in the myelin membrane.1fv1: STRUCTURAL BASIS FOR THE BINDING OF AN IMMUNODOMINANT PEPTIDE FROM MYELIN BASIC PROTEIN IN DIFFERENT REGISTERS BY TWO HLA-DR2 ALLELES1bx2: CRYSTAL STRUCTURE OF HLA-DR2 (DRA*0101,DRB1*1501) COMPLEXED WITH A PEPTIDE FROM HUMAN MYELIN BASIC PROTEIN1hqr: CRYSTAL STRUCTURE OF A SUPERANTIGEN BOUND TO THE HIGH-AFFINITY, ZINC-DEPENDENT SITE ON MHC CLASS II1ymm: TCR/HLA-DR2b/MBP-peptide complex 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. MBP maintains the correct structure of myelin, interacting with the lipids in the myelin membrane. MBP was initially sequenced in 1971 after isolation from bovine myelin membranes. 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; 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. 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. 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. 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. They were 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. 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. 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%.