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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) | ||||||
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![]() | RIBOSOME / translational pausing / XBP1 / UPR | ||||||
機能・相同性 | ![]() epithelial cell maturation involved in salivary gland development / positive regulation of protein acetylation / ATF6-mediated unfolded protein response / response to insulin-like growth factor stimulus / positive regulation of vascular wound healing / glandular epithelial cell maturation / sterol homeostasis / positive regulation of lactation / IRE1alpha activates chaperones / ATF6 (ATF6-alpha) activates chaperone genes ...epithelial cell maturation involved in salivary gland development / positive regulation of protein acetylation / ATF6-mediated unfolded protein response / response to insulin-like growth factor stimulus / positive regulation of vascular wound healing / glandular epithelial cell maturation / sterol homeostasis / positive regulation of lactation / IRE1alpha activates chaperones / ATF6 (ATF6-alpha) activates chaperone genes / positive regulation of plasma cell differentiation / positive regulation of phospholipid biosynthetic process / positive regulation of ERAD pathway / negative regulation of myotube differentiation / intracellular triglyceride homeostasis / cellular response to fructose stimulus / cellular response to laminar fluid shear stress / XBP1(S) activates chaperone genes / cellular response to nutrient / exocrine pancreas development / cellular response to fluid shear stress / positive regulation of MHC class II biosynthetic process / negative regulation of endoplasmic reticulum unfolded protein response / positive regulation of vascular associated smooth muscle cell migration / endothelial cell proliferation / ribosomal subunit / positive regulation of hepatocyte proliferation / cellular response to peptide hormone stimulus / exit from mitosis / positive regulation of T cell differentiation / positive regulation of B cell differentiation / optic nerve development / positive regulation of immunoglobulin production / retinal ganglion cell axon guidance / muscle organ development / negative regulation of SMAD protein signal transduction / IRE1-mediated unfolded protein response / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / positive regulation of endothelial cell apoptotic process / cellular response to vascular endothelial growth factor stimulus / phagocytic cup / positive regulation of TOR signaling / 90S preribosome / positive regulation of fat cell differentiation / adipose tissue development / fatty acid homeostasis / vascular endothelial growth factor receptor signaling pathway / neuron development / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / endoplasmic reticulum unfolded protein response / cellular response to glucose starvation / cis-regulatory region sequence-specific DNA binding / ribosomal small subunit export from nucleus / rough endoplasmic reticulum / translation regulator activity / positive regulation of vascular associated smooth muscle cell proliferation / ERAD pathway / positive regulation of autophagy / gastrulation / MDM2/MDM4 family protein binding / cytosolic ribosome / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / cellular response to interleukin-4 / response to endoplasmic reticulum stress / cellular response to leukemia inhibitory factor / cholesterol homeostasis / liver development / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / positive regulation of apoptotic signaling pathway / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / RNA polymerase II transcription regulatory region sequence-specific DNA binding / nuclear estrogen receptor binding / maturation of SSU-rRNA / phosphatidylinositol 3-kinase/protein kinase B signal transduction / cellular response to amino acid stimulus / small-subunit processome / regulation of cell growth / negative regulation of transforming growth factor beta receptor signaling pathway / cellular response to glucose stimulus / protein destabilization / negative regulation of ERK1 and ERK2 cascade / regulation of protein stability / chromatin DNA binding / autophagy / positive regulation of interleukin-6 production / spindle / mRNA 5'-UTR binding / RNA polymerase II transcription regulator complex / positive regulation of protein import into nucleus / cellular response to insulin stimulus / positive regulation of angiogenesis / rRNA processing / fatty acid biosynthetic process / sequence-specific double-stranded DNA binding / rhythmic process / positive regulation of canonical Wnt signaling pathway 類似検索 - 分子機能 | ||||||
生物種 | ![]() ![]() ![]() ![]() ![]() | ||||||
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 | ||||||
![]() | Shanmuganathan, V. / Cheng, J. / Berninghausen, O. / Beckmann, R. | ||||||
資金援助 | ![]()
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![]() | ![]() 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 |
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 4.7 MB | 表示 | ![]() |
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PDB形式 | ![]() | 表示 | ![]() | |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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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) ![]() ![]() |
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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) ![]() ![]() |
#3: RNA鎖 | 分子量: 50143.648 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() |
#49: RNA鎖 | 分子量: 24414.496 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() |
#50: RNA鎖 | 分子量: 24148.355 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() |
#51: RNA鎖 | 分子量: 548024.188 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() |
#85: RNA鎖 | 分子量: 3145.932 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) ![]() |
+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) ![]() ![]() |
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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) ![]() ![]() |
#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) ![]() ![]() |
#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) ![]() ![]() |
#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) ![]() ![]() |
#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) ![]() ![]() |
#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) ![]() ![]() |
+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) ![]() ![]() ![]() |
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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) ![]() ![]() |
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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) ![]() ![]() |
#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) ![]() ![]() |
#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) ![]() ![]() |
#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) ![]() ![]() |
#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) ![]() ![]() |
#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) ![]() ![]() |
#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) ![]() ![]() |
-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 |
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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 |
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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: ![]() |
電子レンズ | モード: BRIGHT FIELD |
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) |
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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 |