Molecular analysis of the binding mode of Toll/interleukin-1 receptor (TIR) domain proteins during TLR2 signaling

Masatoshi Nada, Hidenori Ohnishi, Hidehito Tochio, Zenichiro Kato, Takeshi Kimura, Kazuo Kubota, Takahiro Yamamoto, Yuji O. Kamatari, Naotaka Tsutsumi, Masahiro Shirakawa, Naomi Kondo

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Toll-like receptor (TLR) signaling is initiated by the binding of various adaptor proteins through ligand-induced oligomerization of the Toll/interleukin-1 receptor (TIR) domains of the TLRs. TLR2, which recognizes peptidoglycans, lipoproteins or lipopeptides derived from Gram-positive bacteria, is known to use the TIR domain-containing adaptor proteins myeloid differentiating factor 88 (MyD88) and MyD88 adaptor-like (Mal). Molecular analyses of the binding specificity of MyD88, Mal, and TLR2 are important for understanding the initial defenses mounted against Gram-positive bacterial infections such as Streptococcus pneumoniae. However, the detailed molecular mechanisms involved in the multiple interactions of these TIR domains remain unclear. Our study demonstrates that the TIR domain proteins MyD88, Mal, TLR1, and TLR2 directly bind to each other in vitro. We have also identified two binding interfaces of the MyD88 TIR domain for the TLR2 TIR domain. A residue at these interfaces has recently been found to be mutated in innate immune deficiency patients. These novel insights into the binding mode of TIR proteins will contribute to elucidation of the mechanisms underlying innate immune deficiency diseases, and to future structural studies of hetero-oligomeric TIR-TIR complexes.

Original languageEnglish
Pages (from-to)108-116
Number of pages9
JournalMolecular Immunology
Issue number3-4
Publication statusPublished - Oct 2012
Externally publishedYes


  • Innate immunity
  • Mal
  • MyD88
  • TIR domain
  • TLR2

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology


Dive into the research topics of 'Molecular analysis of the binding mode of Toll/interleukin-1 receptor (TIR) domain proteins during TLR2 signaling'. Together they form a unique fingerprint.

Cite this