ИСТИНА

Proteasomes are protein complexes located in the nucleus and the cytoplasm of all eukaryotes and some bacteria. Their main function is proteolysis of unneeded or damaged proteins. It is established that ubiquitin-proteasome system participates in pathogenesis of several neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and Huntington's disease. In the case of the latter one mutant proteins with an elongated polyglutamine fragment are formed and cannot be effectively degraded by the proteasome. Thus it is important to study how the proteasome can be activated in the case of such substrates. The complex responsible for protein cleavage in cells is 26S proteasome which represents 20S proteasome associated with 19S regulator particle. Another reguator protein – 11S – is known to increase peptidase activity of 20S proteasome. We studied how 11S protein affects on the cleavage by 20S and 26S proteasomes of different peptide substrates containing oligoglutamine fragments of various length. Also we examined dependence of hydrolysis rate on molar ratio of 11S protein to proteasome and determined preferable sites of proteasomal cleavage. It was found that 11S regulator particle increases only 20S proteasome activity in the case of short substrates with 5 glutamine residues but for longer substrates with 10 glutamine residues it increases hydrolysis rate by both 20S and 26S proteasomes. Thus one may conclude that hybrid proteasome complexes 19S-20S-11S can effectively degrade substrates of enough length even with oligoglutamine fragment. This work was supported by the Russian Foundation for Basic Research project № 16-04-01446.