Crystal structure of TIR domain of TLR6 reveals novel dimeric interface of TIR-TIR interaction for toll-like receptor signaling pathway

J Mol Biol. 2014 Sep 23;426(19):3305-3313. doi: 10.1016/j.jmb.2014.07.024. Epub 2014 Jul 31.

Abstract

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.

Keywords: NF-kappaB; TIR domain; TLR6; crystal structure; innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Genetic Vectors
  • Humans
  • Membrane Glycoproteins / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Receptors, Interleukin-1 / chemistry*
  • Signal Transduction
  • Toll-Like Receptor 6 / chemistry*
  • Toll-Like Receptor 6 / ultrastructure

Substances

  • Membrane Glycoproteins
  • Receptors, Interleukin-1
  • TIRAP protein, human
  • TLR6 protein, human
  • Toll-Like Receptor 6

Associated data

  • PDB/4OM7