ISDA: 8W8M

Deposition Date 2023-09-04

Release Date 2024-09-04

Last Version Date 2026-05-06

Entry Detail

PDB ID:

8W8M

Keywords:

IMMUNE SYSTEM

Title:

Cryo-EM structure of helical filament of MyD88 TIR

Biological Source:

Source Organism(s):

Homo sapiens (Taxon ID: 9606)

Expression System(s):

Escherichia coli

Method Details:

Experimental Method:

ELECTRON MICROSCOPY

Resolution:

3.28 Å

Aggregation State:

HELICAL ARRAY

Reconstruction Method:

SINGLE PARTICLE

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Macromolecular Entities

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:Myeloid differentiation prima
Gene (Uniprot):MYD88
Chain IDs:A (auth: D2), B (auth: D3), C (auth: E1), D (auth: E2), E (auth: E3), F (auth: F1), G (auth: F2), H (auth: F3), I (auth: D1), J (auth: A2), K (auth: A3), L (auth: B1), M (auth: B2), N (auth: B3), O (auth: C1), P (auth: C2), Q (auth: C3), R (auth: A1), S (auth: J2), T (auth: J3), U (auth: K1), V (auth: K2), W (auth: K3), X (auth: L1), Y (auth: L2), Z (auth: L3), AA (auth: J1), BA (auth: G2), CA (auth: G3), DA (auth: H1), EA (auth: H2), FA (auth: H3), GA (auth: I1), HA (auth: I2), IA (auth: I3), JA (auth: G1), KA (auth: M2), LA (auth: M3), MA (auth: N1), NA (auth: N2), OA (auth: N3), PA (auth: O1), QA (auth: O2), RA (auth: O3), SA (auth: M1), TA (auth: P2), UA (auth: P3), VA (auth: Q1), WA (auth: Q2), XA (auth: Q3), YA (auth: R1), ZA (auth: R2), AB (auth: R3), BB (auth: P1), CB (auth: S2), DB (auth: S3), EB (auth: T1), FB (auth: T2), GB (auth: T3), HB (auth: U1), IB (auth: U2), JB (auth: U3), KB (auth: S1), LB (auth: V2), MB (auth: V3), NB (auth: W1), OB (auth: W2), PB (auth: W3), QB (auth: X1), RB (auth: X2), SB (auth: X3), TB (auth: V1), UB (auth: Y2), VB (auth: Y3), WB (auth: Z1), XB (auth: Z2), YB (auth: Z3), ZB (auth: 1A), AC (auth: 2A), BC (auth: 3A), CC (auth: Y1), DC (auth: 2B), EC (auth: 3B), FC (auth: 1C), GC (auth: 2C), HC (auth: 3C), IC (auth: 1D), JC (auth: 2D), KC (auth: 3D), LC (auth: 1B), MC (auth: ZD), NC (auth: YE), OC (auth: ZE), PC (auth: 1E), QC (auth: YF), RC (auth: ZF), SC (auth: 1F), TC (auth: YD), UC (auth: 2E), VC (auth: 3E), WC (auth: 2F), XC (auth: 3F)
Chain Length:144
Number of Molecules:102
Biological Source:Homo sapiens

UniProt ID:Q99836 Pfam ID:PF13676

Ligand Molecules

Primary Citation

Structural Mechanism of Receptor-Triggered MyD88 Oligomeric Assembly in Innate Immune Signaling.

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.Show

Nat Commun ? ? ? (2026)

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

Abstact

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(MyD88)) is responsible for this receptor-mediated oligomerization, but the detailed mechanism involved remains elusive. Here we investigate the structure of TIR(MyD88) oligomers and their interactions with TLRs. Cryoelectron microscopy reveals that tandemly arrayed TIR(MyD88) subunits form an antiparallel double-stranded filament that can further form rings and cylindrical filaments. Moreover, the self-assembly of TIR(MyD88) 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(MyD88), in addition to its direct interaction with the receptor TIRs. These results reveal a regulatory mechanism of TIR(MyD88) oligomerization underlying the signal initiation step.

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