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Differences in Susceptibility of MBP Charge Isomers to Digestion by Stromelysin-1 (MMP-3) and Release of an Immunodominant Epitope

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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.

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Acknowledgments

We thank Teresa Miani for expert technical assistance with preparation of myelin basic protein. This work was supported by a grant from the CIHR and the MS Society of Canada to M.A.M. Partial funding by the MS Society of Canada through a studentship to C.A.D. is appreciated.

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Authors and Affiliations

  1. Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Cres. West, Toronto, M5S 3H2, Canada

    Cheryl A. D’Souza

  2. Department of Structural Biology and Biochemistry, Hospital for Sick Children, M5G 1X8, Toronto, Canada

    Mario A. Moscarello

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  1. Cheryl A. D’Souza
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  2. Mario A. Moscarello
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Correspondence to Cheryl A. D’Souza.

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D’Souza, C.A., Moscarello, M.A. Differences in Susceptibility of MBP Charge Isomers to Digestion by Stromelysin-1 (MMP-3) and Release of an Immunodominant Epitope. Neurochem Res 31, 1045–1054 (2006). https://doi.org/10.1007/s11064-006-9116-9

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