+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6r6p | ||||||
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タイトル | Structure of XBP1u-paused ribosome nascent chain complex (rotated state) | ||||||
要素 |
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キーワード | RIBOSOME (リボソーム) / translational pausing / XBP1 (XBP1) / UPR | ||||||
機能・相同性 | 機能・相同性情報 ATF6-mediated unfolded protein response / positive regulation of protein acetylation / organelle organization / response to insulin-like growth factor stimulus / positive regulation of vascular wound healing / positive regulation of plasma cell differentiation / positive regulation of ERAD pathway / positive regulation of lactation / IRE1alpha activates chaperones / sterol homeostasis ...ATF6-mediated unfolded protein response / positive regulation of protein acetylation / organelle organization / response to insulin-like growth factor stimulus / positive regulation of vascular wound healing / positive regulation of plasma cell differentiation / positive regulation of ERAD pathway / positive regulation of lactation / IRE1alpha activates chaperones / sterol homeostasis / ATF6 (ATF6-alpha) activates chaperone genes / cellular response to fructose stimulus / : / positive regulation of phospholipid biosynthetic process / negative regulation of myotube differentiation / intracellular triglyceride homeostasis / XBP1(S) activates chaperone genes / negative regulation of endoplasmic reticulum unfolded protein response / cellular response to laminar fluid shear stress / cellular response to nutrient / ERAD pathway / positive regulation of endothelial cell apoptotic process / cellular response to fluid shear stress / positive regulation of MHC class II biosynthetic process / positive regulation of endoplasmic reticulum unfolded protein response / positive regulation of vascular associated smooth muscle cell migration / endothelial cell proliferation / positive regulation of hepatocyte proliferation / ribosomal subunit / muscle organ development / positive regulation of T cell differentiation / cellular response to peptide hormone stimulus / regulation of G1 to G0 transition / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / negative regulation of DNA repair / positive regulation of B cell differentiation / oxidized purine DNA binding / G1 to G0 transition / supercoiled DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / NF-kappaB complex / negative regulation of phagocytosis / ubiquitin-like protein conjugating enzyme binding / IRE1-mediated unfolded protein response / neuron development / protein kinase A binding / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / positive regulation of immunoglobulin production / positive regulation of activated T cell proliferation / positive regulation of TOR signaling / BH3 domain binding / positive regulation of fat cell differentiation / fatty acid homeostasis / cysteine-type endopeptidase activator activity involved in apoptotic process / ribosomal small subunit export from nucleus / cellular response to glucose starvation / cellular response to vascular endothelial growth factor stimulus / adipose tissue development / translation regulator activity / cis-regulatory region sequence-specific DNA binding / cellular response to actinomycin D / vascular endothelial growth factor receptor signaling pathway / positive regulation of autophagy / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / 小胞体 / endoplasmic reticulum unfolded protein response / gastrulation / spindle assembly / signaling adaptor activity / MDM2/MDM4 family protein binding / : / positive regulation of vascular associated smooth muscle cell proliferation / rescue of stalled ribosome / negative regulation of smoothened signaling pathway / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / negative regulation of ubiquitin-dependent protein catabolic process / negative regulation of peptidyl-serine phosphorylation / response to endoplasmic reticulum stress / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / cytosolic ribosome / positive regulation of intrinsic apoptotic signaling pathway / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / positive regulation of microtubule polymerization / ribosomal large subunit biogenesis 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Oryctolagus cuniculus (ウサギ) Saccharomyces cerevisiae (パン酵母) | ||||||
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: 3.1 Å | ||||||
データ登録者 | Shanmuganathan, V. / Cheng, J. / Berninghausen, O. / Beckmann, R. | ||||||
資金援助 | ドイツ, 1件
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引用 | ジャーナル: Elife / 年: 2019 タイトル: Structural and mutational analysis of the ribosome-arresting human XBP1u. 著者: Vivekanandan Shanmuganathan / Nina Schiller / Anastasia Magoulopoulou / Jingdong Cheng / Katharina Braunger / Florian Cymer / Otto Berninghausen / Birgitta Beatrix / Kenji Kohno / Gunnar von ...著者: Vivekanandan Shanmuganathan / Nina Schiller / Anastasia Magoulopoulou / Jingdong Cheng / Katharina Braunger / Florian Cymer / Otto Berninghausen / Birgitta Beatrix / Kenji Kohno / Gunnar von Heijne / Roland Beckmann / 要旨: XBP1u, a central component of the unfolded protein response (UPR), is a mammalian protein containing a functionally critical translational arrest peptide (AP). Here, we present a 3 Å cryo-EM ...XBP1u, a central component of the unfolded protein response (UPR), is a mammalian protein containing a functionally critical translational arrest peptide (AP). Here, we present a 3 Å cryo-EM structure of the stalled human XBP1u AP. It forms a unique turn in the ribosomal exit tunnel proximal to the peptidyl transferase center where it causes a subtle distortion, thereby explaining the temporary translational arrest induced by XBP1u. During ribosomal pausing the hydrophobic region 2 (HR2) of XBP1u is recognized by SRP, but fails to efficiently gate the Sec61 translocon. An exhaustive mutagenesis scan of the XBP1u AP revealed that only 8 out of 20 mutagenized positions are optimal; in the remaining 12 positions, we identify 55 different mutations increase the level of translational arrest. Thus, the wildtype XBP1u AP induces only an intermediate level of translational arrest, allowing efficient targeting by SRP without activating the Sec61 channel. | ||||||
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 | 6r6p.cif.gz | 4.7 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6r6p.ent.gz | 表示 | PDB形式 | |
PDBx/mmJSON形式 | 6r6p.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/r6/6r6p ftp://data.pdbj.org/pub/pdb/validation_reports/r6/6r6p | HTTPS FTP |
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-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
-RNA鎖 , 7種, 7分子 57823K4
#1: RNA鎖 | 分子量: 1186579.500 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) |
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#2: RNA鎖 | 分子量: 38691.914 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) |
#3: RNA鎖 | 分子量: 50143.648 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) |
#49: RNA鎖 | 分子量: 24414.496 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Saccharomyces cerevisiae (パン酵母) |
#50: RNA鎖 | 分子量: 24148.355 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Saccharomyces cerevisiae (パン酵母) |
#51: RNA鎖 | 分子量: 548024.188 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) |
#85: RNA鎖 | 分子量: 3145.932 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) |
+タンパク質 , 41種, 41分子 ABCFGHJOPQRSTVXacdefghkmorsqvMM...
-60S ribosomal protein ... , 7種, 7分子 DELZbin
#7: タンパク質 | 分子量: 34006.312 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1SYJ6 |
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#8: タンパク質 | 分子量: 28529.848 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1TG04 |
#14: タンパク質 | 分子量: 24216.525 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1TPV0 |
#28: タンパク質 | 分子量: 15704.635 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1TXF6 |
#30: タンパク質 | 分子量: 8706.283 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1TN82 |
#37: タンパク質 | 分子量: 11888.371 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1TTQ5 |
#42: タンパク質・ペプチド | 分子量: 3213.075 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: A0A087WNH4 |
+Ribosomal protein ... , 21種, 21分子 IMNUWYjlptXXEEQQUUTTVVDDBBOOFF6
-タンパク質・ペプチド , 1種, 1分子 1
#48: タンパク質・ペプチド | 分子量: 2895.380 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: XBP1, TREB5, XBP2 / 発現宿主: Oryctolagus cuniculus (ウサギ) / 参照: UniProt: P17861 |
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-40S ribosomal protein ... , 8種, 8分子 uxzyCCJJAARR
#53: タンパク質 | 分子量: 24759.145 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1SS70 |
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#55: タンパク質 | 分子量: 29523.674 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1TK17 |
#56: タンパク質 | 分子量: 27471.535 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1TM55 |
#57: タンパク質 | 分子量: 21629.309 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1SVB0 |
#58: タンパク質 | 分子量: 24003.012 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1TJW1 |
#70: タンパク質 | 分子量: 9348.990 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1TZ76 |
#71: タンパク質 | 分子量: 6317.539 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1T8A2 |
#75: タンパク質 | 分子量: 13048.244 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1SFR8 |
-非ポリマー , 2種, 164分子
#86: 化合物 | ChemComp-MG / #87: 化合物 | ChemComp-ZN / |
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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: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 |
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由来(天然) |
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由来(組換発現) |
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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 |
-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: SPOT SCAN |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy |
撮影 | 電子線照射量: 28 e/Å2 フィルム・検出器のモデル: FEI FALCON II (4k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: NONE | |||||||||||||||
対称性 | 点対称性: C1 (非対称) | |||||||||||||||
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: 94923 / 対称性のタイプ: POINT | |||||||||||||||
原子モデル構築 | プロトコル: RIGID BODY FIT |