title: Differences in susceptibility of MBP charge isomers to digestion by stromelysin-1 (MMP-3) and release of an immunodominant epitope.
abstract: Charge microheterogeneity of myelin basic protein is known to affect its conformation and function. Here, the citrullinated myelin basic protein charge isomer, component-8, was shown to be more susceptible to stromelysin-1 cleavage than myelin basic protein component-1. Since levels of component-8 are increased in multiple sclerosis brain, the increased susceptibility of component-8 to proteolytic digestion may play a role in the pathogenesis of multiple sclerosis. Interestingly, component-1 isolated from multiple sclerosis patients was digested at a faster rate by stromelysin-1 than component-1 isolated from normal individuals. The reason for this difference is not clear, but likely reflects conformational differences between the two proteins as a result of post-translational modifications. Stromelysin-1 was able to cleave myelin basic protein in the presence of lipids and within the context of myelin and released several peptides including peptides containing the immunodominant epitope.
authors.affiliation: Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen's Park Cres. West, Toronto, M5S 3H2, Canada. cheryl.dsouza@utoronto.ca
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: D'Souza
authors.forename: Mario A
authors.initials: MA
authors.lastname: Moscarello
mesh_terms: D000818:Animals; D002417:Cattle; D006801:Humans; D016056:Immunodominant Epitopes; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000378:metabolism; D004676:Myelin Basic Protein / Q000737:chemistry / Q000378:metabolism; D009186:Myelin Sheath / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism
chemical_list: D016056:Immunodominant Epitopes; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D020033:Protein Isoforms; D019278:Matrix Metalloproteinase 3