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

• Published in: Journal of molecular biology 2014-09, Vol.426 (19), p.3305-3313
• Main Authors: Jang, Tae-ho, Park, Hyun Ho
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Binding Sites; Cloning, Molecular; crystal structure; Crystallography, X-Ray; Escherichia coli - genetics; Escherichia coli - metabolism; Gene Expression; Genetic Vectors; Humans; innate immunity; Membrane Glycoproteins - chemistry; Models, Molecular; Molecular Sequence Data; NF-kappaB; Protein Structure, Tertiary; Receptors, Interleukin-1 - chemistry; Signal Transduction; TIR domain; TLR6; Toll-Like Receptor 6 - chemistry; Toll-Like Receptor 6 - ultrastructure
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2014.07.024

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