8YYM

Cryo-EM structure of cylindrical fiber of MyD88 TIR

This is a non-PDB format compatible entry.

Summary for 8YYM

• Entry DOI: 10.2210/pdb8yym/pdb
• Related: 8W8M
• EMDB information: 37355 39676
• Descriptor: Myeloid differentiation primary response protein MyD88 (1 entity in total)
• Functional Keywords: signaling protein, innate immunity, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 104
• Total formula weight: 1751544.60

Authors

Kasai, K.,Imamura, K.,Narita, A.,Makino, F.,Miyata, T.,Kato, T.,Namba, K.,Onishi, H.,Tochio, H. (deposition date: 2024-04-04, release date: 2025-03-26, Last modification date: 2026-05-06)

Primary citation

Kasai, K.,Imamura, K.,Uno, M.,Nukui, S.,Sekiyama, N.,Miyata, T.,Makino, F.,Yamada, R.,Takahashi, Y.,Kodera, N.,Namba, K.,Ohnishi, H.,Narita, A.,Konno, H.,Tochio, H.
Structural Mechanism of Receptor-Triggered MyD88 Oligomeric Assembly in Innate Immune Signaling.
Nat Commun, 2026

PubMed 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 (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.

PubMed: 41997963
DOI: 10.1038/s41467-026-71836-8

Experimental method

ELECTRON MICROSCOPY (3.3 Å)