+
Open data
-
Basic information
| Entry | Database: PDB / ID: 8yym | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Title | Cryo-EM structure of cylindrical fiber of MyD88 TIR | |||||||||||||||||||||
Components | Myeloid differentiation primary response protein MyD88 | |||||||||||||||||||||
Keywords | IMMUNE SYSTEM / signaling protein / innate immunity | |||||||||||||||||||||
| Function / homology | Function and homology informationMyD88 deficiency (TLR5) / Toll binding / toll-like receptor 5 signaling pathway / ATP-dependent histone chaperone activity / TIR domain binding / toll-like receptor 8 signaling pathway / positive regulation of interleukin-23 production / IRAK4 deficiency (TLR5) / DEx/H-box helicases activate type I IFN and inflammatory cytokines production / MyD88 dependent cascade initiated on endosome ...MyD88 deficiency (TLR5) / Toll binding / toll-like receptor 5 signaling pathway / ATP-dependent histone chaperone activity / TIR domain binding / toll-like receptor 8 signaling pathway / positive regulation of interleukin-23 production / IRAK4 deficiency (TLR5) / DEx/H-box helicases activate type I IFN and inflammatory cytokines production / MyD88 dependent cascade initiated on endosome / cellular response to oxidised low-density lipoprotein particle stimulus / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / Toll-like receptor binding / MyD88 cascade initiated on plasma membrane / toll-like receptor TLR6:TLR2 signaling pathway / Toll signaling pathway / interleukin-33-mediated signaling pathway / regulation of MAP kinase activity / NLRP3 inflammasome complex assembly / defense response to protozoan / RIP-mediated NFkB activation via ZBP1 / death receptor binding / MyD88 deficiency (TLR2/4) / interleukin-1 receptor binding / response to amine / positive regulation of interleukin-17 production / interleukin-1-mediated signaling pathway / toll-like receptor 4 signaling pathway / 3'-UTR-mediated mRNA stabilization / positive regulation of cytokine production involved in inflammatory response / IRAK4 deficiency (TLR2/4) / extrinsic component of plasma membrane / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / skin development / MyD88-dependent toll-like receptor signaling pathway / extrinsic component of cytoplasmic side of plasma membrane / toll-like receptor signaling pathway / type I interferon-mediated signaling pathway / positive regulation of NLRP3 inflammasome complex assembly / response to amino acid / JNK cascade / phagocytosis / canonical NF-kappaB signal transduction / positive regulation of type I interferon production / gene expression / positive regulation of smooth muscle cell proliferation / signaling adaptor activity / response to interleukin-1 / p75NTR recruits signalling complexes / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / positive regulation of interleukin-8 production / positive regulation of interleukin-1 beta production / cellular response to mechanical stimulus / positive regulation of interleukin-6 production / Interleukin-1 signaling / PIP3 activates AKT signaling / cellular response to lipopolysaccharide / regulation of inflammatory response / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / ER-Phagosome pathway / defense response to virus / molecular adaptor activity / response to ethanol / positive regulation of canonical NF-kappaB signal transduction / cell surface receptor signaling pathway / defense response to bacterium / defense response to Gram-positive bacterium / endosome membrane / innate immune response / apoptotic process / positive regulation of gene expression / cell surface / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||||||||||||||
| Biological species | Homo sapiens (human) | |||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||||||||||||||
Authors | Kasai, K. / Imamura, K. / Narita, A. / Makino, F. / Miyata, T. / Kato, T. / Namba, K. / Onishi, H. / Tochio, H. | |||||||||||||||||||||
| Funding support | Japan, 2items
| |||||||||||||||||||||
Citation | Journal: Nat Commun / Year: 2026Title: Structural Mechanism of Receptor-Triggered MyD88 Oligomeric Assembly in Innate Immune Signaling. Authors: Kazuki Kasai / Kayo Imamura / Masatoshi Uno / Shiho Nukui / Naotaka Sekiyama / Tomoko Miyata / Fumiaki Makino / Ryusei Yamada / Yoshiki Takahashi / Noriyuki Kodera / Keiichi Namba / Hidenori ...Authors: 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 / ![]() 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 ...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. #1: Journal: Biorxiv / Year: 2024Title: From Monomers to Oligomers: Structural Mechanism of Receptor-Triggered MyD88 Assembly in Innate Immune Signaling Authors: Kasai, K. / Imamura, K. / Uno, M. / Sekiyama, N. / Miyata, T. / Makino, F. / Yamada, R. / Takahashi, Y. / Kodera, N. / Namba, K. / Ohnishi, H. / Narita, A. / Konno, H. / Tochio, H. | |||||||||||||||||||||
| History |
|
-
Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
|---|
-
Downloads & links
-
Download
| PDBx/mmCIF format | 8yym.cif.gz | 2.4 MB | Display | PDBx/mmCIF format |
|---|---|---|---|---|
| PDB format | pdb8yym.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 8yym.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yy/8yym ftp://data.pdbj.org/pub/pdb/validation_reports/yy/8yym | HTTPS FTP |
|---|
-Related structure data
| Related structure data | ![]() 39676MC ![]() 8w8mC C: citing same article ( M: map data used to model this data |
|---|---|
| Similar structure data | Similarity search - Function & homology F&H Search |
-
Links
-
Assembly
| Deposited unit | ![]()
|
|---|---|
| 1 |
|
-
Components
| #1: Protein | Mass: 16841.775 Da / Num. of mol.: 104 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MYD88 / Production host: ![]() Has protein modification | N | |
|---|
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
|---|---|
| EM experiment | Aggregation state: HELICAL ARRAY / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
| Component | Name: signaling adopter protein in a self-assembled form / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Molecular weight | Value: 5.7 kDa/nm / Experimental value: YES | ||||||||||||||||||||
| Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||||||
| Source (recombinant) | Organism: ![]() | ||||||||||||||||||||
| Buffer solution | pH: 7 | ||||||||||||||||||||
| Buffer component |
| ||||||||||||||||||||
| Specimen | Conc.: 3.4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||
| Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-
Electron microscopy imaging
| Microscopy | Model: JEOL CRYO ARM 300 |
|---|---|
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm |
| Image recording | Average exposure time: 3.2 sec. / Electron dose: 1 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of real images: 5325 |
-
Processing
| EM software | Name: Gctf / Category: CTF correction | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CTF correction | Type: NONE | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 26680 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refinement | Stereochemistry target values: CDL v1.2 | ||||||||||||||||||||||||
| Refine LS restraints |
|
Movie
Controller
About Yorodumi




Homo sapiens (human)
Japan, 2items
Citation


PDBj












FIELD EMISSION GUN