+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7c77 | ||||||
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タイトル | Cryo-EM structure of mouse TLR3 in complex with UNC93B1 | ||||||
要素 |
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キーワード | IMMUNE SYSTEM / Toll-like receptors / UNC93B1 / MFS | ||||||
機能・相同性 | 機能・相同性情報 Trafficking and processing of endosomal TLR / type III interferon production / positive regulation of type III interferon production / response to dsRNA / T cell antigen processing and presentation / toll-like receptor 7 signaling pathway / regulation of dendritic cell cytokine production / inflammatory response to wounding / Toll-like receptor binding / toll-like receptor 3 signaling pathway ...Trafficking and processing of endosomal TLR / type III interferon production / positive regulation of type III interferon production / response to dsRNA / T cell antigen processing and presentation / toll-like receptor 7 signaling pathway / regulation of dendritic cell cytokine production / inflammatory response to wounding / Toll-like receptor binding / toll-like receptor 3 signaling pathway / necroptotic signaling pathway / toll-like receptor 9 signaling pathway / early phagosome / positive regulation of cytokine production involved in inflammatory response / positive regulation of macrophage cytokine production / cellular response to exogenous dsRNA / pattern recognition receptor activity / toll-like receptor signaling pathway / response to exogenous dsRNA / positive regulation of interferon-alpha production / antigen processing and presentation / positive regulation of type I interferon production / cellular response to interferon-beta / positive regulation of chemokine production / extrinsic apoptotic signaling pathway / JNK cascade / positive regulation of interleukin-12 production / positive regulation of interferon-beta production / positive regulation of interleukin-8 production / intracellular protein transport / positive regulation of JNK cascade / microglial cell activation / response to virus / cell morphogenesis / cellular response to type II interferon / cellular response to virus / defense response / cellular response to mechanical stimulus / positive regulation of interleukin-6 production / positive regulation of type II interferon production / positive regulation of non-canonical NF-kappaB signal transduction / male gonad development / positive regulation of angiogenesis / antigen processing and presentation of exogenous peptide antigen via MHC class II / positive regulation of tumor necrosis factor production / double-stranded RNA binding / MAPK cascade / transmembrane signaling receptor activity / cellular response to xenobiotic stimulus / signaling receptor activity / defense response to virus / positive regulation of canonical NF-kappaB signal transduction / lysosome / early endosome / endosome membrane / endosome / inflammatory response / positive regulation of apoptotic process / innate immune response / endoplasmic reticulum membrane / cell surface / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / identical protein binding / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | Mus musculus (ハツカネズミ) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.3 Å | ||||||
データ登録者 | Ohto, U. / Ishida, H. / Shimizu, T. | ||||||
引用 | ジャーナル: Nat Struct Mol Biol / 年: 2021 タイトル: Cryo-EM structures of Toll-like receptors in complex with UNC93B1. 著者: Hanako Ishida / Jinta Asami / Zhikuan Zhang / Tomohiro Nishizawa / Hideki Shigematsu / Umeharu Ohto / Toshiyuki Shimizu / 要旨: Nucleic acid-sensing Toll-like receptors (TLRs) play a pivotal role in innate immunity by recognizing foreign DNA and RNA. Compartmentalization of these TLRs in the endosome limits their activation ...Nucleic acid-sensing Toll-like receptors (TLRs) play a pivotal role in innate immunity by recognizing foreign DNA and RNA. Compartmentalization of these TLRs in the endosome limits their activation by self-derived nucleic acids and reduces the possibility of autoimmune reactions. Although chaperone Unc-93 homolog B1, TLR signaling regulator (UNC93B1) is indispensable for the trafficking of TLRs from the endoplasmic reticulum to the endosome, mechanisms of UNC93B1-mediated TLR regulation remain largely unknown. Here, we report two cryo-EM structures of human and mouse TLR3-UNC93B1 complexes and a human TLR7-UNC93B1 complex. UNC93B1 exhibits structural similarity to the major facilitator superfamily transporters. Both TLRs interact with the UNC93B1 amino-terminal six-helix bundle through their transmembrane and luminal juxtamembrane regions, but the complexes of TLR3 and TLR7 with UNC93B1 differ in their oligomerization state. The structural information provided here should aid in designing compounds to combat autoimmune diseases. | ||||||
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 | 7c77.cif.gz | 230.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7c77.ent.gz | 180.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7c77.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 | 7c77_validation.pdf.gz | 1.1 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7c77_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | 7c77_validation.xml.gz | 37.4 KB | 表示 | |
CIF形式データ | 7c77_validation.cif.gz | 56.1 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/c7/7c77 ftp://data.pdbj.org/pub/pdb/validation_reports/c7/7c77 | 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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-要素
#1: タンパク質 | 分子量: 103785.797 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: Tlr3 / 細胞株 (発現宿主): Expi293F / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q99MB1 | ||||||
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#2: タンパク質 | 分子量: 67039.250 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: Unc93b1, Unc93b / 細胞株 (発現宿主): Expi293F / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q8VCW4 | ||||||
#3: 多糖 | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | ||||||
#4: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #5: 糖 | ChemComp-NAG / 研究の焦点であるリガンドがあるか | N | Has protein modification | Y | |
-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: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Complex of TLR3 and UNC93B1 / タイプ: COMPLEX / Entity ID: #1-#2 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Mus musculoides (ネズミ) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) / 細胞: Expi293F |
緩衝液 | pH: 7.5 / 詳細: 25 mM Hepes-NaOH, pH 7.5, 0.2 M NaCl, and 0.01% GDN |
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 |
-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: OTHER |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 60 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
CTF補正 | タイプ: NONE |
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3次元再構成 | 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 72000 / 対称性のタイプ: POINT |