MAPPIT analysis of TLR adaptor complexes

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

Keywords: Toll-like receptor, MAPPIT, Signal transduction