The proteasome is a high molecular protein complex whose purpose is specific protein degradation in eukaryotic cells. One of the proteasome functions is to produce peptides, which will then be presented on the outer cell membrane using main histocompatibility complex (MHc) molecules of the first or second class. there are definite reasons to believe that proteasome directly takes part in the specific degradation of myelin basic protein (MBP), which make up to 30% of all proteins in the myelin sheath of neuronal axons. the details of the proteasomal degradation of MBP are still unclear. In this work, the features of specific MBP degradation by proteasome were studied. It was demonstrated that MBP (non-ubiquitinated) is a good substrate for 20S and for the 26S proteasome. this is the first work on detecting the sites of MBP proteolysis by proteasome from brains of SJL/J/J and Balb/c mice’s lines. Substantial differences in the degradation pattern of this neuroantigen were found, which could indicate the better presentation MBP parts on MHc molecules in the case of mice predisposed to the development of experimental autoimmune encephalomyelitis.
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INTRODuCTION which will then be presented on the cell membrane using Multiple sclerosis (MS) – a chronic neurodegenerative main histocompatibility complex (MHc) molecules of the disease of autoimmune nature – is an outstanding med-first or second class [10]. there are definite reasons to asical–social problem, because it affects mainly the young sume that proteasome directly takes part in specific MBP and middle-aged. the problem of MS treatment still has degradation. the details of this process are still unclear. no satisfactory solution, and to this day there are several In this work, the specific features of MBP degradation by medicines (therapies) able to suppress MS to some extent, proteasome were studied. but not to fully cure it. neuronal degradation occurs in the It is well-known that the 20S proteasome (a multicatabrain of MS patients due to the destruction of the neuron’s lytic proteinase complex) is an oligomeric high-molecularmyelin sheath. One biochemical characteristic which dif-weight (700 kDa) proteinase that can be isolated separately. ferentiates myelin from other biological membranes is the this complex is the catalytic core of the larger 26S proteas-high lipid/protein ratio. Proteins comprise 25–30% of the ome, which also contains one or two regulatory 19S subunits. mass of the myelin sheath dry matter. About 30% of all It was shown that both 20S and 26S proteasomes are able myelin proteins are three isoforms of the myelin basic pro-to degrade proteins, including the MBP [11, 12]. the questein (MBP). MBP is one of the main autoantigen in MS. ear-tion of the site-specificity of MBP degradation by the prolier, we and other authors showed that catalytic antibodies teasome remained open. It is also known that, during many [2–5] and some proteases [6–9] may be involved in MBP inflammatory pathological processes, the standard protease degradation. It is known that every eukaryotic cell contains complex (constitutive proteasome) transforms into a form a special compartment for targeted protein degradation of immunoproteasome, which has an alternative specificity (proteasome), which is a high molecular protease complex. and catalytic efficiency with respect to intracellular proteins One of the proteasome's functions is to produce peptides, processing. It is very likely that this ‘switching’ is closely
Moscow State University; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Chemistry Department
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