Biophysical Society Thematic Meeting - October 13-15, 2015

Biophysics of Proteins at Surfaces: Assembly, Activation, Signaling

Poster Abstracts

14-POS Board 14 Apotope Recognition by Anti-TRIM21 Autoantibodies in Systemic Lupus Erythematosus N.M. Nascimento 1 , I.S. Monzó 1 , M.A. Gonzalez-Martínez 1 , S. Morais 1 , R. Puchades 1 , A. Maquieira 1 , David Gimenez-Romero 2 . 1 Department of Chemistry, Universitat Politècnica de València, Camino de Vera, Valencia 46022, Spain, 2 Department of Physical Chemistry, Universitat de València, Avda. Dr. Moliner 50, 46100 Burjassot, Spain. Systemic lupus erythematosus (SLE) is related to autoimmune diseases that share several genetic and phenotypic features. TRIM21 is a characteristic autoantigen in SLE patients, although it has not been addressed how this protein regulates this pathology. To investigate this association, we studied the recombinant human antigen TRIM21-IgG molecular recognition. QCM-based studies indicated TRIM21-IgG interactions in SLE patients occurs by an antibody bipolar bridging mechanism. These studies also confirms that the anti-TRIM21 serum only accelerates the formation of the resulting complex, remaining unchanged the TRIM21 biological function in SLE patients and control subjects. The peptide array-based epitope mapping indicates that the major linear human epitope of anti-TRIM21 serum spans the amino acid sequence LRRKQELAE. This epitope has been confirmed by computational prediction of major histocompatibility complex class II binding regions in antigenic protein sequences, which exclusively focused on solvent-accessible residues. For that, the structure homology modelling for TRIM21 was made. In view of that, the mechanism by which TRIM21 may link to the SLE is clarified. We hypothesized that circulating autoantibodies interact with apotope of the TRIM21 protein when this one translocates from the cytoplasm to cell surface. The anti-TRIM21 serum only reinforces the “sensor” (immune signal induction) function of TRIM21 in translocated cells through the TRIM21-anchored Ub-63Ub chains, leading to tissue inflammation and systemic autoimmunity. According to our experimental data, we can relate the presence of anti-TRIM21 autoantibodies in SLE patients with skin, heart and brain disorders, where this protein has been observed in plasma membrane-localized form in many studies. Acknowledgements We acknowledges financial support from the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund under award number CTQ2013-42914-R. Furthermore, Noelle M. do Nascimento acknowledges the fellowship from the Generalitat Valenciana (GRISOLIA/2012/024).

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