+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7beq | ||||||
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タイトル | MicroED structure of the MyD88 TIR domain higher-order assembly | ||||||
要素 | Myeloid differentiation primary response protein MyD88 | ||||||
キーワード | PROTEIN BINDING / MicroED / MyD88 / TIR domain / higher-order assembly | ||||||
機能・相同性 | 機能・相同性情報 regulation of chemokine (C-X-C motif) ligand 1 production / Toll binding / MyD88 deficiency (TLR5) / regulation of chemokine (C-X-C motif) ligand 2 production / ATP-dependent histone chaperone activity / neutrophil-mediated killing of bacterium / 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 / Toll binding / MyD88 deficiency (TLR5) / regulation of chemokine (C-X-C motif) ligand 2 production / ATP-dependent histone chaperone activity / neutrophil-mediated killing of bacterium / 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 / positive regulation of interleukin-23 production / establishment of endothelial intestinal barrier / IRAK4 deficiency (TLR5) / regulation of neutrophil migration / cellular response to oxidised low-density lipoprotein particle stimulus / MyD88 dependent cascade initiated on endosome / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / MyD88 cascade initiated on plasma membrane / Toll signaling pathway / Toll-like receptor binding / DEx/H-box helicases activate type I IFN and inflammatory cytokines production / neutrophil activation involved in immune response / interleukin-33-mediated signaling pathway / microglia differentiation / RIP-mediated NFkB activation via ZBP1 / positive regulation of cytokine production involved in inflammatory response / death receptor binding / interleukin-1 receptor binding / MyD88 deficiency (TLR2/4) / positive regulation of macrophage cytokine production / MyD88-dependent toll-like receptor signaling pathway / interleukin-1-mediated signaling pathway / IRAK4 deficiency (TLR2/4) / 3'-UTR-mediated mRNA stabilization / skin development / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / toll-like receptor 4 signaling pathway / positive regulation of NLRP3 inflammasome complex assembly / extrinsic component of plasma membrane / type I interferon-mediated signaling pathway / defense response to protozoan / positive regulation of interleukin-17 production / response to amine / immunoglobulin mediated immune response / positive regulation of type I interferon production / response to amino acid / phagocytosis / signaling adaptor activity / positive regulation of chemokine production / JNK cascade / lipopolysaccharide-mediated signaling pathway / extrinsic component of cytoplasmic side of plasma membrane / 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 / Interleukin-1 signaling / cellular response to mechanical stimulus / : / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / PIP3 activates AKT signaling / positive regulation of NF-kappaB transcription factor activity / gene expression / ER-Phagosome pathway / regulation of inflammatory response / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / cellular response to lipopolysaccharide / positive regulation of canonical NF-kappaB signal transduction / response to ethanol / defense response to virus / molecular adaptor activity / cell surface receptor signaling pathway / endosome membrane / defense response to Gram-positive bacterium / defense response to bacterium / 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 / cytoplasm / cytosol 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | 電子線結晶学 / 分子置換 / クライオ電子顕微鏡法 / 解像度: 3 Å | ||||||
データ登録者 | Clabbers, M.T.B. / Holmes, S. / Muusse, T.W. / Vajjhala, P. / Thygesen, S.J. / Malde, A.K. / Hunter, D.J.B. / Croll, T.I. / Nanson, J.D. / Rahaman, M.H. ...Clabbers, M.T.B. / Holmes, S. / Muusse, T.W. / Vajjhala, P. / Thygesen, S.J. / Malde, A.K. / Hunter, D.J.B. / Croll, T.I. / Nanson, J.D. / Rahaman, M.H. / Aquila, A. / Hunter, M.S. / Liang, M. / Yoon, C.H. / Zhao, J. / Zatsepin, N.A. / Abbey, B. / Sierecki, E. / Gambin, Y. / Darmanin, C. / Kobe, B. / Xu, H. / Ve, T. | ||||||
資金援助 | スウェーデン, 1件
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引用 | ジャーナル: Nat Commun / 年: 2021 タイトル: MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography. 著者: Max T B Clabbers / Susannah Holmes / Timothy W Muusse / Parimala R Vajjhala / Sara J Thygesen / Alpeshkumar K Malde / Dominic J B Hunter / Tristan I Croll / Leonie Flueckiger / Jeffrey D ...著者: Max T B Clabbers / Susannah Holmes / Timothy W Muusse / Parimala R Vajjhala / Sara J Thygesen / Alpeshkumar K Malde / Dominic J B Hunter / Tristan I Croll / Leonie Flueckiger / Jeffrey D Nanson / Md Habibur Rahaman / Andrew Aquila / Mark S Hunter / Mengning Liang / Chun Hong Yoon / Jingjing Zhao / Nadia A Zatsepin / Brian Abbey / Emma Sierecki / Yann Gambin / Katryn J Stacey / Connie Darmanin / Bostjan Kobe / Hongyi Xu / Thomas Ve / 要旨: MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production. We previously observed that the TIR domain of MAL (MAL) forms filaments in vitro and ...MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production. We previously observed that the TIR domain of MAL (MAL) forms filaments in vitro and induces formation of crystalline higher-order assemblies of the MyD88 TIR domain (MyD88). These crystals are too small for conventional X-ray crystallography, but are ideally suited to structure determination by microcrystal electron diffraction (MicroED) and serial femtosecond crystallography (SFX). Here, we present MicroED and SFX structures of the MyD88 assembly, which reveal a two-stranded higher-order assembly arrangement of TIR domains analogous to that seen previously for MAL. We demonstrate via mutagenesis that the MyD88 assembly interfaces are critical for TLR4 signaling in vivo, and we show that MAL promotes unidirectional assembly of MyD88. Collectively, our studies provide structural and mechanistic insight into TLR signal transduction and allow a direct comparison of the MicroED and SFX techniques. | ||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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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 | 7beq.cif.gz | 49.6 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7beq.ent.gz | 26.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7beq.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 | 7beq_validation.pdf.gz | 407.5 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7beq_full_validation.pdf.gz | 408 KB | 表示 | |
XML形式データ | 7beq_validation.xml.gz | 6.9 KB | 表示 | |
CIF形式データ | 7beq_validation.cif.gz | 8.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/be/7beq ftp://data.pdbj.org/pub/pdb/validation_reports/be/7beq | HTTPS FTP |
-関連構造データ
関連構造データ | 7berC 7l6wC 4w8gS S: 精密化の開始モデル C: 同じ文献を引用 (文献) |
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類似構造データ | |
実験データセット #1 | データ参照: 10.15785/SBGRID/814 / データの種類: diffraction image data |
-リンク
-集合体
登録構造単位 |
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単位格子 |
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-要素
#1: タンパク質 | 分子量: 17833.854 Da / 分子数: 1 / 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 BL21(DE3) (大腸菌) / 参照: UniProt: Q99836 |
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-実験情報
-実験
実験 | 手法: 電子線結晶学 |
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EM実験 | 試料の集合状態: 3D ARRAY / 3次元再構成法: 電子線結晶学 |
-試料調製
構成要素 | 名称: Myeloid differentiation primary response protein MyD88 タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 値: 0.018 MDa / 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Escherichia coli BL21(DE3) (大腸菌) |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-データ収集
顕微鏡 | モデル: JEOL 2100 |
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電子銃 | 電子線源: LAB6 / 加速電圧: 200 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: DIFFRACTION |
撮影 | 電子線照射量: 0.08 e/Å2 / フィルム・検出器のモデル: OTHER |
EM回折 | カメラ長: 1830 mm |
EM回折 シェル | 解像度: 30.54→3 Å / フーリエ空間範囲: 73.7 % / 多重度: 12.2 / 構造因子数: 2436 / 位相残差: 1 ° |
EM回折 統計 | フーリエ空間範囲: 73.7 % / 再高解像度: 3 Å / 測定した強度の数: 29803 / 構造因子数: 2436 / 位相誤差: 22.11 ° / 位相残差: 1 ° / 位相誤差の除外基準: 1 / Rmerge: 0.459 / Rsym: 0.459 |
反射 | Biso Wilson estimate: 64.03 Å2 |
-解析
ソフトウェア |
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EM 3D crystal entity | ∠α: 90 ° / ∠β: 107.7 ° / ∠γ: 90 ° / A: 99.06 Å / B: 31.01 Å / C: 54.3 Å / 空間群名: C2 / 空間群番号: 5 | ||||||||||||||||||||||||
CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度の算出法: DIFFRACTION PATTERN/LAYERLINES / 対称性のタイプ: 3D CRYSTAL | ||||||||||||||||||||||||
原子モデル構築 | プロトコル: OTHER | ||||||||||||||||||||||||
精密化 | 構造決定の手法: 分子置換 開始モデル: 4W8G 解像度: 3→30.54 Å / SU ML: 0 / 交差検証法: THROUGHOUT / σ(F): 1.36 / 位相誤差: 22.1064 / 立体化学のターゲット値: CDL v1.2
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溶媒の処理 | 減衰半径: 0.9 Å / VDWプローブ半径: 1.11 Å / 溶媒モデル: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 52.01 Å2 | ||||||||||||||||||||||||
精密化ステップ | サイクル: LAST / 解像度: 3→30.54 Å
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拘束条件 |
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LS精密化 シェル | 解像度: 3→30.54 Å
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