| | MAPPIT analysis of TLR adaptor complexesEdited by Giulio Superti-Furga Received 26 October 2006; received in revised form 22 December 2006; accepted 11 January 2007. published online 18 January 2007. Abstract Toll-like receptors (TLRs) are crucial components of the innate immune system, coupling pathogen recognition to a cellular response. We used the MAPPIT mammalian two-hybrid technique to investigate protein–protein interactions in the early steps in TLR signalling. A partial TLR-adaptor interaction map was constructed confirming several known but also documenting novel interactions. We show that the TLR adaptor Mal is critical for linking Myeloid Differentiation primary response protein 88 (MyD88) to TLR2 and TLR4. Analysis of the contributions of the different sub-domains of MyD88-adaptor-like protein (Mal) and MyD88 in adaptor homo- and hetero-dimerisation provides an initial mechanistic insight in this bridging function of Mal. Abbreviations: IFN, interferon, LR, Leptin receptor, Mal, MyD88-adaptor-like protein, MyD88, Myeloid Differentiation primary response protein 88, Sarm, Sterile alpha and HEAT-Armadillo motifs containing protein, STAT, Signal Transducer and Activator of Transcription, TIR, Toll/IL-1 Receptor, TLR, Toll-like receptor, Tram, TRIF-related adaptor molecule, Trif, TIR-domain containing adaptor inducing IFNβ a Flanders Institute for Biotechnology (VIB), Department of Medical Protein Research, Faculty of Medicine and Health Sciences, Ghent University, A. Baertsoenkaai 3, B-9000 Ghent, Belgium b Flanders Institute for Biotechnology (VIB), Department for Molecular Biomedical Research, Faculty of Sciences, Ghent University, Technologiepark, B-9052 Gent, Belgium Corresponding author. Fax: +32 9 2649492.
PII: S0014-5793(07)00050-6 doi:10.1016/j.febslet.2007.01.026 © 2007 Federation of European Biochemical Societies | |
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