- EMDB-4745: Structure of XBP1u-paused ribosome nascent chain complex with Sec61. -
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基本情報
登録情報
データベース: EMDB / ID: EMD-4745
タイトル
Structure of XBP1u-paused ribosome nascent chain complex with Sec61.
マップデータ
Structure of XBP1u-paused ribosome nascent chain complex with Sec61.
試料
複合体: Structure of XBP1u-paused ribosome nascent chain complex with Sec61.
複合体: Ribosome
タンパク質・ペプチド: x 77種
RNA: x 4種
細胞器官・細胞要素: X-box-binding protein 1
タンパク質・ペプチド: x 1種
細胞器官・細胞要素: tRNA
RNA: x 2種
細胞器官・細胞要素: Sec61
タンパク質・ペプチド: x 3種
細胞器官・細胞要素: mRNA
RNA: x 1種
リガンド: x 2種
キーワード
translational pausing / XBP1 / UPR / RIBOSOME
機能・相同性
機能・相同性情報
epithelial cell maturation involved in salivary gland development / positive regulation of protein acetylation / ATF6-mediated unfolded protein response / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / membrane docking / response to insulin-like growth factor stimulus / positive regulation of vascular wound healing / glandular epithelial cell maturation / sterol homeostasis / positive regulation of lactation ...epithelial cell maturation involved in salivary gland development / positive regulation of protein acetylation / ATF6-mediated unfolded protein response / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / membrane docking / 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 / endoplasmic reticulum Sec complex / positive regulation of plasma cell differentiation / pronephric nephron development / positive regulation of phospholipid biosynthetic process / positive regulation of ERAD pathway / negative regulation of myotube differentiation / intracellular triglyceride homeostasis / cotranslational protein targeting to membrane / Ssh1 translocon complex / Sec61 translocon complex / protein targeting to ER / protein insertion into ER membrane / protein-transporting ATPase activity / cellular response to fructose stimulus / cellular response to laminar fluid shear stress / XBP1(S) activates chaperone genes / SRP-dependent cotranslational protein targeting to membrane, translocation / cellular response to nutrient / signal sequence binding / 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 / post-translational protein targeting to membrane, translocation / 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 / protein transmembrane transporter 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 / guanyl-nucleotide exchange factor activity / 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 類似検索 - 分子機能
: / Protein transport Sec61-beta/Sbh / Protein transport protein SecG/Sec61-beta/Sbh / Sec61beta family / Protein translocase SEC61 complex, gamma subunit / Protein translocase SecE domain superfamily / Translocon Sec61/SecY, plug domain / Plug domain of Sec61p / Protein secE/sec61-gamma signature. / Protein secY signature 1. ...: / Protein transport Sec61-beta/Sbh / Protein transport protein SecG/Sec61-beta/Sbh / Sec61beta family / Protein translocase SEC61 complex, gamma subunit / Protein translocase SecE domain superfamily / Translocon Sec61/SecY, plug domain / Plug domain of Sec61p / Protein secE/sec61-gamma signature. / Protein secY signature 1. / Protein secY signature 2. / SecE/Sec61-gamma subunits of protein translocation complex / Protein translocase complex, SecE/Sec61-gamma subunit / SecY/SEC61-alpha family / SecY domain superfamily / SecY conserved site / SecY / Basic region leucine zipper / Basic-leucine zipper (bZIP) domain signature. / Basic-leucine zipper (bZIP) domain profile. / basic region leucin zipper / Basic-leucine zipper domain / Basic-leucine zipper domain superfamily / 60S acidic ribosomal protein P0 / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ubiquitin-like protein FUBI / Ribosomal protein L30e / Ribosomal protein L2, archaeal-type / Ribosomal L15/L27a, N-terminal / Ribosomal protein L28e / Ribosomal protein L23 / 60S ribosomal protein L10P, insertion domain / Insertion domain in 60S ribosomal protein L10P / Ribosomal L28e/Mak16 / Ribosomal L28e protein family / metallochaperone-like domain / TRASH domain / Ribosomal protein L41 / Ribosomal protein L41 / : / Ribosomal protein S12e signature. / Ribosomal protein S12e / Ribosomal protein L29e / Ribosomal L29e protein family / Ribosomal protein S19e, conserved site / Ribosomal protein S19e signature. / Small (40S) ribosomal subunit Asc1/RACK1 / S27a-like superfamily / Ribosomal protein L10e, conserved site / Ribosomal protein L10e signature. / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein L10e / 40S Ribosomal protein S10 / : / Ribosomal protein S7e signature. / Ribosomal protein L44e signature. / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / : / Ribosomal protein L6e signature. / Ribosomal protein S8e subdomain, eukaryotes / Ribosomal protein S25 / S25 ribosomal protein / Ribosomal protein S27a / Ribosomal protein S17e, conserved site / : / Ribosomal protein S27a / Ribosomal protein S17e signature. / Ribosomal protein S27a / Ribosomal protein S3Ae, conserved site / Ribosomal protein S3Ae signature. / Ribosomal protein L44e / Ribosomal protein S30 / Ribosomal protein L44 / Ribosomal protein S30 / Ribosomal protein L34e, conserved site / Ribosomal protein L34e signature. / Ribosomal protein L5 eukaryotic, C-terminal / Ribosomal L18 C-terminal region / Ribosomal protein L30e signature 1. / 40S ribosomal protein S29/30S ribosomal protein S14 type Z / Ribosomal protein S27e signature. / 40S ribosomal protein S4, C-terminal domain / 40S ribosomal protein S4 C-terminus / Ribosomal protein S4e, N-terminal, conserved site / Ribosomal protein S4e signature. / Ribosomal protein L23/L25, N-terminal / : / Ribosomal protein L23, N-terminal domain / Ribosomal protein S3, eukaryotic/archaeal / Eukaryotic Ribosomal Protein L27, KOW domain / Ribosomal protein 60S L18 and 50S L18e / Ribosomal Protein L6, KOW domain / Ribosomal protein L18/L18-A/B/e, conserved site / Ribosomal protein L18e signature. / Ribosomal protein L30e signature 2. 類似検索 - ドメイン・相同性
Small ribosomal subunit protein eS32 / Large ribosomal subunit protein uL16 / Small ribosomal subunit protein uS4 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein eL33 / Small ribosomal subunit protein eS12 / Large ribosomal subunit protein eL29 / Small ribosomal subunit protein uS9 ...Small ribosomal subunit protein eS32 / Large ribosomal subunit protein uL16 / Small ribosomal subunit protein uS4 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein eL33 / Small ribosomal subunit protein eS12 / Large ribosomal subunit protein eL29 / Small ribosomal subunit protein uS9 / Large ribosomal subunit protein eL31 / Large ribosomal subunit protein eL21 / Large ribosomal subunit protein uL29 / Small ribosomal subunit protein RACK1 / Ubiquitin-ribosomal protein eS31 fusion protein / Large ribosomal subunit protein eL6 / Large ribosomal subunit protein uL11 / Large ribosomal subunit protein uL15 / Small ribosomal subunit protein uS15 / Large ribosomal subunit protein uL24 / Small ribosomal subunit protein eS1 / Large ribosomal subunit protein eL8 / Large ribosomal subunit protein uL30 / Small ribosomal subunit protein eS7 / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein eL43 / Large ribosomal subunit protein uL18 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein uS13 / Large ribosomal subunit protein eL42 / Large ribosomal subunit protein eL15 / Large ribosomal subunit protein uL14 / Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein / Small ribosomal subunit protein eS25 / Large ribosomal subunit protein eL30 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein eS28 / Small ribosomal subunit protein eS8 / Small ribosomal subunit protein eS4 / Large ribosomal subunit protein uL3 / Small ribosomal subunit protein eS6 / Small ribosomal subunit protein eS19 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein uS13 / Uncharacterized protein / Small ribosomal subunit protein eS10 / Small ribosomal subunit protein uS17 / Large ribosomal subunit protein uL2 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein eL36 / Small ribosomal subunit protein eS17 / Large ribosomal subunit protein uL5 / Large ribosomal subunit protein eL32 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein uL15/eL18 domain-containing protein / Large ribosomal subunit protein eL27 / Small ribosomal subunit protein eS27 / Small ribosomal subunit protein uS19 / 60S acidic ribosomal protein P0 / Large ribosomal subunit protein eL28 / Small ribosomal subunit protein uS14 / Large ribosomal subunit protein eL34 / X-box-binding protein 1 / Protein transport protein Sec61 subunit alpha isoform 1 / Protein transport protein Sec61 subunit gamma / Protein transport protein Sec61 subunit beta / Large ribosomal subunit protein eL14 / Large ribosomal subunit protein eL37 類似検索 - 構成要素
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.