Databases and computational interaction models of toll-like receptors [Elektronische Ressource] / vorgelegt von Jing Gong

Databases and computational interaction models of Toll-like receptors Dissertation Fakultät für Geowissenschaften Ludwig-Maximilians-Universität München vorgelegt von Jing Gong München, den 24. Februar 2010 Erstgutachter: Prof. Dr. Wolfgang M. Heckl Zweitgut. Robert W. Stark Prüfungstermin: 26.05.2010 Abstract Abstract Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) on invading organisms and are the first line of defense in innate immunity. To date, much has been learned about TLRs and their roles in autoimmune diseases are being unraveled. The autoimmune disease systemic lupus erythematosus (SLE) progresses as a consequence of the inappropriate recognition of self nucleic acids by TLRs. For the development of therapeutic approaches of SLE it is necessary to understand possible negative regulation mechanisms of TLR. Single immunoglobulin interleukin-1 receptor-related molecule (SIGIRR) is the best characterized TLR signaling inhibitor. It can interfere with the receptor complexes and attenuate the recruitment of downstream adaptors to the receptors. So far, the mechanisms of structural interactions between SIGIRR, TLRs and adaptor molecules are unknown. To develop a working hypothesis for these interactions, we constructed three- dimensional models for these single molecules based on computational predictions.