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TitleStructural Mechanism of Receptor-Triggered MyD88 Oligomeric Assembly in Innate Immune Signaling.
Journal, issue, pagesNat Commun, Year 2026
Publish dateApr 17, 2026
AuthorsKazuki 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 /
PubMed AbstractMyD88 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 ...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 (TIR) is responsible for this receptor-mediated oligomerization, but the detailed mechanism involved remains elusive. Here we investigate the structure of TIR oligomers and their interactions with TLRs. Cryoelectron microscopy reveals that tandemly arrayed TIR subunits form an antiparallel double-stranded filament that can further form rings and cylindrical filaments. Moreover, the self-assembly of TIR 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 TIR, in addition to its direct interaction with the receptor TIRs. These results reveal a regulatory mechanism of TIR oligomerization underlying the signal initiation step.
External linksNat Commun / PubMed:41997963
MethodsEM (single particle)
Resolution3.28 - 3.3 Å
Structure data

37355

8w8m

EMDB-37355, PDB-8w8m:
Cryo-EM structure of helical filament of MyD88 TIR
Method: EM (single particle) / Resolution: 3.28 Å

39676

8yym

EMDB-39676, PDB-8yym:
Cryo-EM structure of cylindrical fiber of MyD88 TIR
Method: EM (single particle) / Resolution: 3.3 Å

Source
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / signaling protein / innate immunity

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