+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6i3n | ||||||
---|---|---|---|---|---|---|---|
タイトル | Helical MyD88 death domain filament | ||||||
要素 | Myeloid differentiation primary response protein MyD88 | ||||||
キーワード | SIGNALING PROTEIN / helix / filament / TLR | ||||||
機能・相同性 | 機能・相同性情報 regulation of chemokine (C-X-C motif) ligand 1 production / neutrophil-mediated killing of bacterium / MyD88 deficiency (TLR5) / regulation of chemokine (C-X-C motif) ligand 2 production / ATP-dependent histone chaperone activity / Toll binding / induced systemic resistance / leukocyte activation involved in inflammatory response / TIR domain binding / response to molecule of fungal origin ...regulation of chemokine (C-X-C motif) ligand 1 production / neutrophil-mediated killing of bacterium / MyD88 deficiency (TLR5) / regulation of chemokine (C-X-C motif) ligand 2 production / ATP-dependent histone chaperone activity / Toll binding / induced systemic resistance / leukocyte activation involved in inflammatory response / TIR domain binding / response to molecule of fungal origin / toll-like receptor 8 signaling pathway / positive regulation of lymphocyte proliferation / response to peptidoglycan / establishment of endothelial intestinal barrier / positive regulation of interleukin-23 production / MyD88 dependent cascade initiated on endosome / IRAK4 deficiency (TLR5) / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / regulation of neutrophil migration / MyD88 cascade initiated on plasma membrane / cellular response to oxidised low-density lipoprotein particle stimulus / Toll signaling pathway / Toll-like receptor binding / DEx/H-box helicases activate type I IFN and inflammatory cytokines production / interleukin-33-mediated signaling pathway / neutrophil activation involved in immune response / microglia differentiation / interleukin-1 receptor binding / RIP-mediated NFkB activation via ZBP1 / positive regulation of cytokine production involved in inflammatory response / death receptor binding / MyD88 deficiency (TLR2/4) / interleukin-1-mediated signaling pathway / MyD88-dependent toll-like receptor signaling pathway / positive regulation of macrophage cytokine production / IRAK4 deficiency (TLR2/4) / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / toll-like receptor 4 signaling pathway / 3'-UTR-mediated mRNA stabilization / skin development / extrinsic component of plasma membrane / positive regulation of NLRP3 inflammasome complex assembly / immune system process / type I interferon-mediated signaling pathway / defense response to protozoan / response to amine / positive regulation of interleukin-17 production / extrinsic component of cytoplasmic side of plasma membrane / positive regulation of type I interferon production / response to amino acid / immunoglobulin mediated immune response / phagocytosis / signaling adaptor activity / lipopolysaccharide-mediated signaling pathway / positive regulation of chemokine production / JNK cascade / p75NTR recruits signalling complexes / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / response to interleukin-1 / positive regulation of interleukin-1 beta production / positive regulation of interleukin-8 production / positive regulation of JNK cascade / positive regulation of smooth muscle cell proliferation / response to organic cyclic compound / cellular response to mechanical stimulus / positive regulation of interleukin-6 production / Interleukin-1 signaling / positive regulation of tumor necrosis factor production / PIP3 activates AKT signaling / positive regulation of NF-kappaB transcription factor activity / ER-Phagosome pathway / regulation of inflammatory response / gene expression / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / cellular response to lipopolysaccharide / defense response to virus / positive regulation of canonical NF-kappaB signal transduction / response to ethanol / molecular adaptor activity / cell surface receptor signaling pathway / endosome membrane / defense response to Gram-positive bacterium / defense response to bacterium / inflammatory response / innate immune response / positive regulation of gene expression / apoptotic process / cell surface / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | 電子顕微鏡法 / らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 3.1 Å | ||||||
データ登録者 | Moncrieffe, M.C. / Bollschweiler, D. / Penczek, P.A.P. / Gay, N.J. | ||||||
引用 | ジャーナル: Structure / 年: 2020 タイトル: MyD88 Death-Domain Oligomerization Determines Myddosome Architecture: Implications for Toll-like Receptor Signaling. 著者: Martin C Moncrieffe / Daniel Bollschweiler / Bing Li / Pawel A Penczek / Lee Hopkins / Clare E Bryant / David Klenerman / Nicholas J Gay / 要旨: Toll-like receptors (TLRs) are pivotal in triggering the innate immune response to pathogen infection. Ligand binding induces receptor dimerization which facilitates the recruitment of other post- ...Toll-like receptors (TLRs) are pivotal in triggering the innate immune response to pathogen infection. Ligand binding induces receptor dimerization which facilitates the recruitment of other post-receptor signal transducers into a complex signalosome, the Myddosome. Central to this process is Myeloid differentiation primary response 88 (MyD88), which is required by almost all TLRs, and signaling is thought to proceed via the stepwise, sequential assembly of individual components. Here, we show that the death domains of human MyD88 spontaneously and reversibly associate to form helical filaments in vitro. A 3.1-Å cryoelectron microscopy structure reveals that the architecture of the filament is identical to that of the 6:4 MyD88-IRAK4-IRAK2 hetero-oligomeric Myddosome. Additionally, the death domain of IRAK4 interacts with the filaments to reconstitute the non-stoichiometric 6:4 MyD88-IRAK4 complex. Together, these data suggest that intracellularly, the MyD88 scaffold may be pre-formed and poised for recruitment of IRAKs on receptor activation and TIR engagement. | ||||||
履歴 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6i3n.cif.gz | 242.1 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb6i3n.ent.gz | 194 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6i3n.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 6i3n_validation.pdf.gz | 1.1 MB | 表示 | wwPDB検証レポート |
---|---|---|---|---|
文書・詳細版 | 6i3n_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | 6i3n_validation.xml.gz | 37.8 KB | 表示 | |
CIF形式データ | 6i3n_validation.cif.gz | 61.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/i3/6i3n ftp://data.pdbj.org/pub/pdb/validation_reports/i3/6i3n | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
|
---|---|
1 |
|
-要素
#1: タンパク質 | 分子量: 17646.873 Da / 分子数: 13 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: MYD88 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: H0Y4G9, UniProt: Q99836*PLUS |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
EM実験 | 試料の集合状態: FILAMENT / 3次元再構成法: らせん対称体再構成法 |
-試料調製
構成要素 | 名称: Human MyD88 / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) | |||||||||||||||
由来(組換発現) | 生物種: Escherichia coli (大腸菌) | |||||||||||||||
緩衝液 | pH: 8 | |||||||||||||||
緩衝液成分 |
| |||||||||||||||
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | |||||||||||||||
試料支持 | グリッドの材料: COPPER / グリッドのタイプ: Quantifoil R1.2/1.3 | |||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 277 K |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 倍率(公称値): 75000 X / 最大 デフォーカス(公称値): 3100 nm / 最小 デフォーカス(公称値): 1000 nm / Calibrated defocus min: 900 nm / 最大 デフォーカス(補正後): 3200 nm / Cs: 2.7 mm / C2レンズ絞り径: 50 µm |
撮影 | 電子線照射量: 0.92 e/Å2 / 検出モード: INTEGRATING フィルム・検出器のモデル: FEI FALCON III (4k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.14rc2_3191: / 分類: 精密化 | ||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EMソフトウェア |
| ||||||||||||||||||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
らせん対称 | 回転角度/サブユニット: 98.01 ° / 軸方向距離/サブユニット: 5.98 Å / らせん対称軸の対称性: C1 | ||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 1229488 / 対称性のタイプ: HELICAL | ||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: OTHER | ||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 3MOP PDB chain-ID: A / Accession code: 3MOP / Source name: PDB / タイプ: experimental model |