2026-05-27 京都大学
MyD88が形作るリング状の多量体構造。左図：高速原子間力顕微鏡（HS-AFM）により捉えた多量体が一部崩壊した後に再構築されていく様子。右図：クライオ電子顕微鏡法（cryo-EM）により明らかになった原子レベルでの多量体の詳細モデル。nm（ナノメートル）は0.000000001ｍのこと。
＜関連情報＞
- https://www.kyoto-u.ac.jp/ja/research-news/2026-05-27-0
- https://www.nature.com/articles/s41467-026-71836-8
自然免疫シグナル伝達における受容体誘導型MyD88多量体形成の構造機構 Structural Mechanism of Receptor-Triggered MyD88 Oligomeric Assembly in Innate Immune Signaling
Kazuki Kasai,Kayo Imamura,Masatoshi Uno,Shiho Nukui,Naotaka Sekiyama,Tomoko Miyata,Fumiaki Makino,Ryusei Yamada,Yoshiki Takahashi,Noriyuki Kodera,Keiichi Namba,Hidenori Ohnishi,Akihiro Narita,Hiroki Konno & Hidehito Tochio
Nature Communications Published:17 April 2026
DOI:https://doi.org/10.1038/s41467-026-71836-8 Unedited version
Abstract
MyD88 plays a pivotal role in Toll-like receptor (TLR) and interleukin-1 family signaling through its oligomerization upon receptor activation, leading to downstream protein recruitment. The Toll/interleukin-1 receptor domain of MyD88 (TIRMyD88) is responsible for this receptor-mediated oligomerization, but the detailed mechanism involved remains elusive. Here we investigate the structure of TIRMyD88 oligomers and their interactions with TLRs. Cryoelectron microscopy reveals that tandemly arrayed TIRMyD88 subunits form an antiparallel double-stranded filament that can further form rings and cylindrical filaments. Moreover, the self-assembly of TIRMyD88 in vitro is markedly accelerated by dimeric rather than monomeric receptor TIRs, possibly reflecting the signal initiation step in vivo. High-speed atomic force microscopy further captures the dynamic processes of oligomerization of TIRMyD88, in addition to its direct interaction with the receptor TIRs. These results reveal a regulatory mechanism of TIRMyD88 oligomerization underlying the signal initiation step.
