Two Be or Not Two Be: The Nuclear Autoantigen La/SS-B Is Able to Form Dimers and Oligomers in a Redox Dependent Manner
| Autor: | Berndt, N., Bippes, C. C., Michalk, I., Bachmann, D., Bachmann, J., Puentes-Cala, E., Bartsch, T., Loureiro, L. R., Kegler, A., Bergmann, R., Gross, J. K., Gross, T., Kurien, B. T., Scofield, R. H., Farris, A. D., James, J. A., Schmitz, M., Fahmy, K., Feldmann, A., Arndt, C., Bachmann, M. |
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| Rok vydání: | 2021 |
| Předmět: |
Polymers
primary Sjögren’s syndrome Autoimmunity Autoantigens Protein Structure Secondary Article lcsh:Chemistry La/SS-B autoantigen Epitopes systemic lupus erythematosus Humans Lupus Erythematosus Systemic anti-La/SS-B antibodies Disulfides lcsh:QH301-705.5 Autoantibodies autoimmunity Temperature RNA-Binding Proteins Recombinant Proteins Oxygen Sjogren's Syndrome lcsh:Biology (General) lcsh:QD1-999 Ribonucleoproteins Antibodies Antinuclear Cytokines RNA Protein Multimerization Oxidation-Reduction |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 7 International Journal of Molecular Sciences, Vol 22, Iss 3377, p 3377 (2021) International Journal of Molecular Sciences 22(2021)7, 3377 |
| ISSN: | 1422-0067 |
| Popis: | According to the literature, the autoantigen La is involved in Cap-independent translation. It was proposed that one prerequisite for this function is the formation of a protein dimer. However, structural analyses argue against La protein dimers. Noteworthy to mention, these structural analyses were performed under reducing conditions. Here we describe that La protein can undergo redox-dependent structural changes. The oxidized form of La protein can form dimers, oligomers and even polymers stabilized by disulfide bridges. The primary sequence of La protein contains three cysteine residues. Only after mutation of all three cysteine residues to alanine La protein becomes insensitive to oxidation, indicating that all three cysteines are involved in redox-dependent structural changes. Biophysical analyses of the secondary structure of La protein support the redox-dependent conformational changes. Moreover, we identified monoclonal anti-La antibodies (anti-La mAbs) that react with either the reduced or oxidized form of La protein. Differential reactivities to the reduced and oxidized form of La protein were also found in anti-La sera of autoimmune patients. |
| Databáze: | OpenAIRE |
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