Two Be or Not Two Be: The Nuclear Autoantigen La/SS-B Is Able to Form Dimers and Oligomers in a Redox Dependent Manner
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...
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| author | Nicole Berndt Claudia C. Bippes Irene Michalk Dominik Bachmann Jennifer Bachmann Edinson Puentes-Cala Tabea Bartsch Liliana R. Loureiro Alexandra Kegler Ralf Bergmann Joanne K. Gross Tim Gross Biji T. Kurien R. Hal Scofield A. Darise Farris Judith A. James Marc Schmitz Karim Fahmy Anja Feldmann Claudia Arndt Michael P. Bachmann |
| author_facet | Nicole Berndt Claudia C. Bippes Irene Michalk Dominik Bachmann Jennifer Bachmann Edinson Puentes-Cala Tabea Bartsch Liliana R. Loureiro Alexandra Kegler Ralf Bergmann Joanne K. Gross Tim Gross Biji T. Kurien R. Hal Scofield A. Darise Farris Judith A. James Marc Schmitz Karim Fahmy Anja Feldmann Claudia Arndt Michael P. Bachmann |
| author_sort | Nicole Berndt |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T12:54:19Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:54:19Z |
| publishDate | 2021-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-84b383b0c42a4df9ac0795ed5eaa295b2023-11-21T12:01:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01227337710.3390/ijms22073377Two Be or Not Two Be: The Nuclear Autoantigen La/SS-B Is Able to Form Dimers and Oligomers in a Redox Dependent MannerNicole Berndt0Claudia C. Bippes1Irene Michalk2Dominik Bachmann3Jennifer Bachmann4Edinson Puentes-Cala5Tabea Bartsch6Liliana R. Loureiro7Alexandra Kegler8Ralf Bergmann9Joanne K. Gross10Tim Gross11Biji T. Kurien12R. Hal Scofield13A. Darise Farris14Judith A. James15Marc Schmitz16Karim Fahmy17Anja Feldmann18Claudia Arndt19Michael P. Bachmann20Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, GermanyInstitute of Immunology, Medical Faculty Carl Gustav Carus Dresden, Technical University Dresden, 01307 Dresden, GermanyInstitute of Immunology, Medical Faculty Carl Gustav Carus Dresden, Technical University Dresden, 01307 Dresden, GermanyUniversity Cancer Center (UCC), Tumor Immunology, University Hospital Carl Gustav Carus Dresden, Technical University Dresden, 01307 Dresden, GermanyUniversity Cancer Center (UCC), Tumor Immunology, University Hospital Carl Gustav Carus Dresden, Technical University Dresden, 01307 Dresden, GermanyDepartment of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, GermanyDepartment of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, GermanyDepartment of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, GermanyDepartment of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, GermanyDepartment of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, GermanyThe Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation and University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAThe Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation and University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAThe Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation and University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAThe Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation and University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAThe Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation and University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAThe Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation and University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAInstitute of Immunology, Medical Faculty Carl Gustav Carus Dresden, Technical University Dresden, 01307 Dresden, GermanyInstitute of Resource Ecology, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, GermanyDepartment of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, GermanyDepartment of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, GermanyDepartment of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, GermanyAccording 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.https://www.mdpi.com/1422-0067/22/7/3377anti-La/SS-B antibodiesautoimmunityLa/SS-B autoantigensystemic lupus erythematosusprimary Sjögren’s syndrome |
| spellingShingle | Nicole Berndt Claudia C. Bippes Irene Michalk Dominik Bachmann Jennifer Bachmann Edinson Puentes-Cala Tabea Bartsch Liliana R. Loureiro Alexandra Kegler Ralf Bergmann Joanne K. Gross Tim Gross Biji T. Kurien R. Hal Scofield A. Darise Farris Judith A. James Marc Schmitz Karim Fahmy Anja Feldmann Claudia Arndt Michael P. Bachmann Two Be or Not Two Be: The Nuclear Autoantigen La/SS-B Is Able to Form Dimers and Oligomers in a Redox Dependent Manner International Journal of Molecular Sciences anti-La/SS-B antibodies autoimmunity La/SS-B autoantigen systemic lupus erythematosus primary Sjögren’s syndrome |
| title | Two Be or Not Two Be: The Nuclear Autoantigen La/SS-B Is Able to Form Dimers and Oligomers in a Redox Dependent Manner |
| title_full | Two Be or Not Two Be: The Nuclear Autoantigen La/SS-B Is Able to Form Dimers and Oligomers in a Redox Dependent Manner |
| title_fullStr | Two Be or Not Two Be: The Nuclear Autoantigen La/SS-B Is Able to Form Dimers and Oligomers in a Redox Dependent Manner |
| title_full_unstemmed | Two Be or Not Two Be: The Nuclear Autoantigen La/SS-B Is Able to Form Dimers and Oligomers in a Redox Dependent Manner |
| title_short | Two Be or Not Two Be: The Nuclear Autoantigen La/SS-B Is Able to Form Dimers and Oligomers in a Redox Dependent Manner |
| title_sort | two be or not two be the nuclear autoantigen la ss b is able to form dimers and oligomers in a redox dependent manner |
| topic | anti-La/SS-B antibodies autoimmunity La/SS-B autoantigen systemic lupus erythematosus primary Sjögren’s syndrome |
| url | https://www.mdpi.com/1422-0067/22/7/3377 |
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