New structural insights into the role of TROVE2 complexes in the on-set and pathogenesis of systemic lupus erythematosus determined by a combination of QCM-D and DPI
| Autor: | Isidro S. Monzó, José Andrés Román-Ivorra, David Giménez-Romero, Noelle M. do Nascimento, José Luis López-Paz, Elena Grau-García, Jorge Escorihuela, Ángel Maquieira, Augusto Juste-Dolz, Rosa Puchades, Sergi Morais |
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| Rok vydání: | 2018 |
| Předmět: |
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Protein Conformation Epitope mapping Fc receptor QCM-D 02 engineering and technology 01 natural sciences Biochemistry Autoantigens Epitope Analytical Chemistry Systemic lupus erythematosus QUIMICA ANALITICA RNA Small Cytoplasmic medicine Humans Lupus Erythematosus Systemic Antibody bipolar bridging Autoantibodies Autoimmune disease biology Chemistry 010401 analytical chemistry Autoantibody TROVE2 021001 nanoscience & nanotechnology medicine.disease Protein tertiary structure Immune complex 0104 chemical sciences Interferometry Ribonucleoproteins Case-Control Studies Dual polarization interferometry Immunology biology.protein Quartz Crystal Microbalance Techniques Female Antibody 0210 nano-technology |
| Zdroj: | RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia instname |
| ISSN: | 1618-2650 |
| Popis: | [EN] The mechanism of self-recognition of the autoantigen TROVE2, a common biomarker in autoimmune diseases, has been studied with a quartz crystal microbalance with dissipation monitoring (QCM-D) and dual polarization interferometry (DPI). The complementarity and remarkable analytical features of both techniques has allowed new insights into the onset of systemic lupus erythematosus (SLE) to be achieved at the molecular level. The in vitro study for SLE patients and healthy subjects suggests that anti-TROVE2 autoantibodies may undergo an antibody bipolar bridging. An epitope-paratope-specific binding initially occurs to activate a hidden Fc receptor in the TROVE2 tertiary structure. This bipolar mechanism may contribute to the pathogenic accumulation of anti-TROVE2 autoantibody immune complex in autoimmune disease. Furthermore, the specific calcium-dependent protein-protein bridges point out at how the TRIM21/TROVE2 association might occur, suggesting that the TROVE2 protein could stimulate the intracellular immune signaling via the TRIM21 PRY-SPRY domain. These findings may help to better understand the origins of the specificity and affinity of TROVE2 interactions, which might play a key role in the SLE pathogenesis. This manuscript gives one of the first practical applications of two novel functions (-df/dD and Delta h/molec) for the analysis of the data provided by QCM-D and DPI. In addition, it is the first time that QCM-D has been used for mapping hidden Fc receptors as well as linear epitopes in a protein tertiary structure. We would like to thank Sylvia Daunert for her invaluable help with the discussion of the paper. Furthermore, we acknowledge financial support from the Generalitat Valenciana (GVA-PROMETEOII/2014/040) as well as the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund under award numbers CTQ2013-45875-R and CTQ2013-42914-R |
| Databáze: | OpenAIRE |
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