Tuusa, J., Raasakka, A., Ruskamo, S. et al. Myelin-derived and putative molecular mimic peptides share structural properties in aqueous and membrane-like environments. Mult Scler Demyelinating Disord 2, 4 (2017). https://doi.org/10.1186/s40893-017-0021-7
Myelin-derived and putative molecular mimic peptides share structural properties in aqueous and membrane-like environments
|Author:||Tuusa, Jussi1; Raasakka, Arne1,2; Ruskamo, Salla1;|
1Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland
2Department of Biomedicine, University of Bergen, Bergen, Norway
|Online Access:||PDF Full Text (PDF, 3.2 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe202103248173
|Publish Date:|| 2021-03-24
Background: Despite intense research, the causes of various neurological diseases remain enigmatic to date. A role for viral or bacterial infection and associated molecular mimicry has frequently been suggested in the etiology of neurological diseases, including demyelinating autoimmune disorders, such as multiple sclerosis. Pathogen mimics of myelin-derived autoimmune peptides have been described in the literature and shown to induce myelin autoimmune responses in animal models.
Methods: We carried out a structural study on myelin-derived peptides, and mimics thereof from various pathogens, in aqueous and membrane-like environments, using conventional and synchrotron radiation circular dichroism spectroscopy. A total of 13 peptides from the literature were studied, and 290 circular dichroism spectra were analysed. In addition, peptide structure predictions and vesicle aggregation assays were performed.
Results: The results indicate a high level of similarity in the biophysical and folding properties of the peptides from either myelin proteins or proteins from pathogenic viruses or bacteria; essentially all of the studied peptides folded in the presence of lipid vesicles or under other membrane-mimicking conditions, which is a sign of membrane interaction. Many of the peptides presented remarkable similarities in their conformation in different environments.
Conclusions: As most of the studied epitope segments in myelin proteins are associated with membrane-binding sites, our results support a view of molecular mimicry, involving lipid membrane interaction propensity and similar conformational properties, possibly playing a role in demyelinating disease. The results suggest mechanisms related to protein amphiphilicity and order-disorder transitions in the recognition of peptide epitopes in autoimmune demyelination.
Multiple sclerosis and demyelinating disorders
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This study has been supported by the Emil Aaltonen Foundation (Finland), the Sigrid Jusélius Foundation (Finland), the Academy of Finland, and the Research Council of Norway (SYNKNØYT program). The funders had no role in the design of the study, the collection, analysis, and interpretation of data, or in writing the manuscript.
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