Differences in Susceptibility of MBP Charge Isomers to Digestion by Stromelysin-1 (MMP-3) and Release of an Immunodominant Epitope |
| |
Authors: | Cheryl A D’Souza Mario A Moscarello |
| |
Institution: | (1) Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Cres. West, Toronto, M5S 3H2, Canada;(2) Department of Structural Biology and Biochemistry, Hospital for Sick Children, M5G 1X8 Toronto, Canada |
| |
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. |
| |
Keywords: | Myelin basic protein Multiple sclerosis Matrix metalloproteinases Stromelysin-1 Immunodominant epitope |
本文献已被 PubMed SpringerLink 等数据库收录! |
|