+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 5uzb | ||||||
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タイトル | Cryo-EM structure of the MAL TIR domain filament | ||||||
要素 | Toll/interleukin-1 receptor domain-containing adapter protein | ||||||
キーワード | IMMUNE SYSTEM / TIR domain / adaptor proteins / TLR signaling / homotypic protein interactions | ||||||
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 / positive regulation of neutrophil chemotaxis / MyD88 deficiency (TLR2/4) / MyD88-dependent toll-like receptor signaling pathway / IRAK4 deficiency (TLR2/4) / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / toll-like receptor 4 signaling pathway / 3'-UTR-mediated mRNA stabilization / regulation of innate immune response / extrinsic component of cytoplasmic side of plasma membrane / cellular response to lipoteichoic acid / endocytic vesicle / signaling adaptor activity / positive regulation of B cell proliferation / phosphatidylinositol-4,5-bisphosphate binding / positive regulation of interleukin-12 production / positive regulation of interleukin-8 production / protein kinase C binding / positive regulation of JNK cascade / ruffle membrane / positive regulation of protein-containing complex assembly / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / positive regulation of NF-kappaB transcription factor activity / protein-macromolecule adaptor activity / positive regulation of canonical NF-kappaB signal transduction / ER-Phagosome pathway / response to lipopolysaccharide / positive regulation of ERK1 and ERK2 cascade / cell surface receptor signaling pathway / molecular adaptor activity / defense response to Gram-positive bacterium / inflammatory response / innate immune response / cell surface / identical protein binding / plasma membrane / cytoplasm / cytosol 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: 7 Å | ||||||
データ登録者 | Ve, T. / Vajjhala, P.R. / Hedger, A. / Croll, T. / DiMaio, F. / Horsefield, S. / Yu, X. / Lavrencic, P. / Hassan, Z. / Morgan, G.P. ...Ve, T. / Vajjhala, P.R. / Hedger, A. / Croll, T. / DiMaio, F. / Horsefield, S. / Yu, X. / Lavrencic, P. / Hassan, Z. / Morgan, G.P. / Mansell, A. / Mobli, M. / O'Carrol, A. / Chauvin, B. / Gambin, Y. / Sierecki, E. / Landsberg, M.J. / Stacey, K.J. / Egelman, E.H. / 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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 5uzb.cif.gz | 331.6 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb5uzb.ent.gz | 272.7 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 5uzb.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 | 5uzb_validation.pdf.gz | 834.9 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 5uzb_full_validation.pdf.gz | 852.3 KB | 表示 | |
XML形式データ | 5uzb_validation.xml.gz | 52.5 KB | 表示 | |
CIF形式データ | 5uzb_validation.cif.gz | 71.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/uz/5uzb ftp://data.pdbj.org/pub/pdb/validation_reports/uz/5uzb | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 19689.162 Da / 分子数: 14 / 断片: UNP residues 79-221 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: TIRAP, MAL / プラスミド: pMCSG7 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P58753 |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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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: MAL TIR domain filament / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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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: 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 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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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 |
試料ホルダ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 20 e/Å2 フィルム・検出器のモデル: FEI FALCON II (4k x 4k) 実像数: 446 |
-解析
EMソフトウェア |
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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: -26.8 ° / 軸方向距離/サブユニット: 15.5 Å / らせん対称軸の対称性: C6 | ||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 7 Å / 解像度の算出法: OTHER / 粒子像の数: 17175 / 対称性のタイプ: HELICAL |