Crystal Structure of TIR Domain of TLR6 Reveals Novel Dimeric Interface of TIR–TIR Interaction for Toll-Like Receptor Signaling Pathway

• TLR6 TIR domain has been successfully purified.
• The first crystal structure of TLR6 TIR domain has been determined at 2.2 Å resolution.
• The structure reveals novel homo-dimeric interfaces, which might be functionally important.

Toll-like receptors (TLRs) are responsible for recognition of particular pathogens during the innate immune response and cytoplasmic Toll/interleukin-1 receptor (TIR) domain responsible for downstream signaling. TLR6 working with TLR2 can detect bacterial lipoprotein leading signal for nuclear factor-kappaB activation for immune response. To better understand TLR-mediated signaling event in the innate immune system, in this study, we report the first crystal structure of the TIR domain of TLR6 at 2.2 Å resolution. Our structure reveals novel homo-dimerization interfaces, which might be a critical for the interaction with TIR-containing adaptor proteins and itself. We also report structural similarities and differences of TLR6 with those of other TIR domains, which may be functionally relevant.

Graphical AbstractNovel homo-demeric interface of TIR domain.Figure optionsDownload high-quality image (135 K)Download as PowerPoint slide