Research Article Glatiramer Acetate and Nanny Proteins Restrict Access of the Multiple Sclerosis Autoantigen Myelin Basic Protein to the 26S Proteasome Ekaterina Kuzina, 1,2 Anna Kudriaeva, 1 Ivan Smirnov, 1,2,3 Michael V. Dubina, 4 Alexander Gabibov, 1,2,3,5 and Alexey Belogurov Jr. 1,3,5 1 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, V-437, Moscow 117871, Russia 2 Chemistry Department, Lomonosov Moscow State University, Moscow 119991, Russia 3 Kazan Federal University, Kazan, Republic of Tatarstan 420008, Russia 4 Nanotechnology Research and Education Centre RAS, St. Petersburg Academic University, St. Petersburg 194021, Russia 5 Institute of Gene Biology, Russian Academy of Sciences, Moscow 117334, Russia Correspondence should be addressed to Alexander Gabibov; gabibov@mx.ibch.ru Received 9 May 2014; Revised 13 August 2014; Accepted 16 August 2014; Published 8 September 2014 Academic Editor: W. David Arnold Copyright © 2014 Ekaterina Kuzina et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We recently showed that myelin basic protein (MBP) is hydrolyzed by 26S proteasome without ubiquitination. Te previously suggested concept of charge-mediated interaction between MBP and the proteasome led us to attempt to compensate or mimic its positive charge to inhibit proteasomal degradation. We demonstrated that negatively charged actin and calmodulin (CaM), as well as basic histone H1.3, inhibit MBP hydrolysis by competing with the proteasome and MBP, respectively, for binding their counterpart. Interestingly, glatiramer acetate (GA), which is used to treat multiple sclerosis (MS) and is structurally similar to MBP, inhibits intracellular and in vitro proteasome-mediated MBP degradation. Terefore, the data reported in this study may be important for myelin biogenesis in both the normal state and pathophysiological conditions. 1. Introduction Myelin basic protein (MBP) is one of the major autoantigens in the pathogenesis of multiple sclerosis (MS) [1] and experi- mental autoimmune encephalomyelitis [2]—animal model of MS. MBP and its peptides have been extensively studied as important components of the autoimmune pathology of the central nervous system (CNS). A number of MBP peptides were found to be strongly associated with MHC class II [3, 4] in MS patients. Although MS is thought to be mainly a CD4+ T cell-mediated disease, myelin-specifc cytotoxic lymphocytes, which recognize MHC I-restricted MBP pep- tides, can lyse human oligodendrocytes in cell culture [5] and cause severe EAE in mice [6]. Te fragments of intracellular proteins that are presented on the MHC class I molecules are generated mainly by the multicatalytic proteinase complex— a 26S proteasome [7]. Te majority of cellular proteins are degraded by the 26S proteasome in a ubiquitin-dependent manner [8]. Te polyubiquitin chains interact with the 19S regulatory particle, which catalyzes the deubiquitination and denaturation of the substrate and its translocation into the 20S catalytic chamber [9, 10]. Interestingly, recent data indicate that proteasome substrates may be polymonoubiq- uitinated [11] or even modifed by single ubiquitin moieties [12]. Moreover, the number of proteins, such as ornithine decarboxylase [13] and p21 [14], can be degraded by the 26S proteasome without ubiquitination in an ATP-dependent manner [15]. Uncapped 20S proteasome particles are also active in the degradation of either completely or regionally disordered nonubiquitinated proteins, such as -synuclein Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 926394, 10 pages http://dx.doi.org/10.1155/2014/926394