+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-8625 | |||||||||
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タイトル | Cryo-EM structure of the MAL TIR domain filament | |||||||||
マップデータ | Cryo-EM structure of the MAL TIR domain filament | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 positive regulation of interleukin-15 production / TIRAP-dependent toll-like receptor 4 signaling pathway / regulation of interferon-beta production / cellular response to bacterial lipopeptide / positive regulation of toll-like receptor 3 signaling pathway / Toll-like receptor 4 binding / positive regulation of toll-like receptor 2 signaling pathway / Toll-like receptor 2 binding / positive regulation of toll-like receptor 4 signaling pathway / positive regulation of chemokine (C-X-C motif) ligand 1 production ...positive regulation of interleukin-15 production / TIRAP-dependent toll-like receptor 4 signaling pathway / regulation of interferon-beta production / cellular response to bacterial lipopeptide / positive regulation of toll-like receptor 3 signaling pathway / Toll-like receptor 4 binding / positive regulation of toll-like receptor 2 signaling pathway / Toll-like receptor 2 binding / positive regulation of toll-like receptor 4 signaling pathway / positive regulation of chemokine (C-X-C motif) ligand 1 production / myeloid cell differentiation / positive regulation of chemokine (C-X-C motif) ligand 2 production / MyD88 deficiency (TLR2/4) / positive regulation of neutrophil chemotaxis / MyD88-dependent toll-like receptor signaling pathway / IRAK4 deficiency (TLR2/4) / regulation of innate immune response / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / toll-like receptor 4 signaling pathway / 3'-UTR-mediated mRNA stabilization / regulation of stress-activated MAPK cascade / cellular response to lipoteichoic acid / endocytic vesicle / canonical NF-kappaB signal transduction / signaling adaptor activity / positive regulation of B cell proliferation / phosphatidylinositol-4,5-bisphosphate binding / extrinsic component of cytoplasmic side of plasma membrane / positive regulation of interleukin-12 production / protein kinase C binding / positive regulation of interleukin-8 production / positive regulation of protein-containing complex assembly / positive regulation of JNK cascade / ruffle membrane / positive regulation of interleukin-6 production / protein-macromolecule adaptor activity / positive regulation of tumor necrosis factor production / positive regulation of NF-kappaB transcription factor activity / ER-Phagosome pathway / positive regulation of canonical NF-kappaB signal transduction / response to lipopolysaccharide / positive regulation of ERK1 and ERK2 cascade / cell surface receptor signaling pathway / molecular adaptor activity / defense response to Gram-positive bacterium / 炎症 / 自然免疫系 / 細胞膜 / identical protein binding / 細胞膜 / 細胞質基質 / 細胞質 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 7.0 Å | |||||||||
データ登録者 | Ve T / Vajjhala PR / Hedger A / Croll T / DiMaio F / Horsefield S / Yu X / Lavrencic P / Hassan Z / Morgan GP ...Ve T / Vajjhala PR / Hedger A / Croll T / DiMaio F / Horsefield S / Yu X / Lavrencic P / Hassan Z / Morgan GP / Mansell A / Mobli M / O'Carrol A / Chauvin B / Gambin Y / Sierecki E / Landsberg MJ / Stacey KJ / Egelman EH / Kobe B | |||||||||
資金援助 | オーストラリア, 1件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2017 タイトル: Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling. 著者: Thomas Ve / Parimala R Vajjhala / Andrew Hedger / Tristan Croll / Frank DiMaio / Shane Horsefield / Xiong Yu / Peter Lavrencic / Zahid Hassan / Garry P Morgan / Ashley Mansell / Mehdi Mobli / ...著者: Thomas Ve / Parimala R Vajjhala / Andrew Hedger / Tristan Croll / Frank DiMaio / Shane Horsefield / Xiong Yu / Peter Lavrencic / Zahid Hassan / Garry P Morgan / Ashley Mansell / Mehdi Mobli / Ailis O'Carroll / Brieuc Chauvin / Yann Gambin / Emma Sierecki / Michael J Landsberg / Katryn J Stacey / Edward H Egelman / Bostjan Kobe / 要旨: Toll-like receptor (TLR) signaling is a key innate immunity response to pathogens. Recruitment of signaling adapters such as MAL (TIRAP) and MyD88 to the TLRs requires Toll/interleukin-1 receptor ...Toll-like receptor (TLR) signaling is a key innate immunity response to pathogens. Recruitment of signaling adapters such as MAL (TIRAP) and MyD88 to the TLRs requires Toll/interleukin-1 receptor (TIR)-domain interactions, which remain structurally elusive. Here we show that MAL TIR domains spontaneously and reversibly form filaments in vitro. They also form cofilaments with TLR4 TIR domains and induce formation of MyD88 assemblies. A 7-Å-resolution cryo-EM structure reveals a stable MAL protofilament consisting of two parallel strands of TIR-domain subunits in a BB-loop-mediated head-to-tail arrangement. Interface residues that are important for the interaction are conserved among different TIR domains. Although large filaments of TLR4, MAL or MyD88 are unlikely to form during cellular signaling, structure-guided mutagenesis, combined with in vivo interaction assays, demonstrated that the MAL interactions defined within the filament represent a template for a conserved mode of TIR-domain interaction involved in both TLR and interleukin-1 receptor signaling. | |||||||||
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 | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_8625.map.gz | 5.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-8625-v30.xml emd-8625.xml | 11.4 KB 11.4 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_8625.png | 77.8 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-8625 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8625 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_8625.map.gz / 形式: CCP4 / 大きさ: 25.8 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Cryo-EM structure of the MAL TIR domain filament | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.07 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
-全体 : MAL TIR domain filament
全体 | 名称: MAL TIR domain filament |
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要素 |
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-超分子 #1: MAL TIR domain filament
超分子 | 名称: MAL TIR domain filament / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Escherichia coli (大腸菌) |
-分子 #1: Toll/interleukin-1 receptor domain-containing adapter protein
分子 | 名称: Toll/interleukin-1 receptor domain-containing adapter protein タイプ: protein_or_peptide / ID: 1 / コピー数: 14 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 19.689162 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: MHHHHHHSSG VDLGTENLYF QSNAEQKLIS EEDLSSRWSK DYDVCVCHSE EDLVAAQDLV SYLEGSTASL RCFLQLRDAT PGGAIVSEL CQALSSSHCR VLLITPGFLQ DPWCKYQMLQ ALTEAPGAEG CTIPLLSGLS RAAYPPELRF MYYVDGRGPD G GFRQVKEA VMRYLQTLS |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | らせん対称体再構成法 |
試料の集合状態 | filament |
-試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | フィルム・検出器のモデル: FEI FALCON II (4k x 4k) 実像数: 446 / 平均電子線量: 20.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
CTF補正 | ソフトウェア - 名称: CTFFIND3 |
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最終 角度割当 | タイプ: NOT APPLICABLE |
最終 再構成 | 想定した対称性 - らせんパラメータ - Δz: 15.5 Å 想定した対称性 - らせんパラメータ - ΔΦ: -26.8 ° 想定した対称性 - らせんパラメータ - 軸対称性: C6 (6回回転対称) 解像度のタイプ: BY AUTHOR / 解像度: 7.0 Å / 解像度の算出法: OTHER / ソフトウェア: (名称: SPIDER, IHRSR) / 使用した粒子像数: 17175 |