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Yorodumi- EMDB-4745: Structure of XBP1u-paused ribosome nascent chain complex with Sec61. -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4745 | |||||||||
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Title | Structure of XBP1u-paused ribosome nascent chain complex with Sec61. | |||||||||
Map data | Structure of XBP1u-paused ribosome nascent chain complex with Sec61. | |||||||||
Sample |
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Function / homology | Function and homology information ATF6-mediated unfolded protein response / positive regulation of protein acetylation / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / response to insulin-like growth factor stimulus / positive regulation of vascular wound healing / membrane docking / organelle organization / positive regulation of plasma cell differentiation / positive regulation of lactation / IRE1alpha activates chaperones ...ATF6-mediated unfolded protein response / positive regulation of protein acetylation / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / response to insulin-like growth factor stimulus / positive regulation of vascular wound healing / membrane docking / organelle organization / positive regulation of plasma cell differentiation / positive regulation of lactation / IRE1alpha activates chaperones / sterol homeostasis / ATF6 (ATF6-alpha) activates chaperone genes / positive regulation of ERAD pathway / endoplasmic reticulum Sec complex / pronephric nephron development / : / positive regulation of phospholipid biosynthetic process / negative regulation of myotube differentiation / intracellular triglyceride homeostasis / cotranslational protein targeting to membrane / Ssh1 translocon complex / Sec61 translocon complex / protein targeting to ER / protein-transporting ATPase activity / cellular response to fructose stimulus / protein insertion into ER membrane / XBP1(S) activates chaperone genes / negative regulation of endoplasmic reticulum unfolded protein response / cellular response to laminar fluid shear stress / cellular response to nutrient / SRP-dependent cotranslational protein targeting to membrane, translocation / cellular response to fluid shear stress / signal sequence binding / positive regulation of endothelial cell apoptotic process / positive regulation of MHC class II biosynthetic process / post-translational protein targeting to membrane, translocation / 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 / ERAD pathway / muscle organ development / positive regulation of T cell differentiation / cellular response to peptide hormone stimulus / positive regulation of B cell differentiation / IRE1-mediated unfolded protein response / protein transmembrane transporter activity / positive regulation of immunoglobulin production / neuron development / positive regulation of TOR signaling / rough endoplasmic reticulum / positive regulation of fat cell differentiation / fatty acid homeostasis / cellular response to vascular endothelial growth factor stimulus / cellular response to glucose starvation / adipose tissue development / cis-regulatory region sequence-specific DNA binding / vascular endothelial growth factor receptor signaling pathway / positive regulation of autophagy / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / endoplasmic reticulum unfolded protein response / positive regulation of vascular associated smooth muscle cell proliferation / cellular response to interleukin-4 / DNA-(apurinic or apyrimidinic site) lyase / response to endoplasmic reticulum stress / cytosolic ribosome / cholesterol homeostasis / liver development / phosphatidylinositol 3-kinase/protein kinase B signal transduction / nuclear estrogen receptor binding / regulation of cell growth / cellular response to glucose stimulus / cellular response to amino acid stimulus / phospholipid binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / negative regulation of transforming growth factor beta receptor signaling pathway / protein destabilization / regulation of protein stability / negative regulation of ERK1 and ERK2 cascade / chromatin DNA binding / autophagy / positive regulation of interleukin-6 production / positive regulation of protein import into nucleus / RNA polymerase II transcription regulator complex / cellular response to insulin stimulus / fatty acid biosynthetic process / positive regulation of angiogenesis / sequence-specific double-stranded DNA binding / ribosome binding / protein transport / ribosome biogenesis / cellular response to oxidative stress / 5S rRNA binding / ubiquitin-dependent protein catabolic process / angiogenesis / cellular response to lipopolysaccharide / protease binding / transcription by RNA polymerase II / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / transcription cis-regulatory region binding Similarity search - Function | |||||||||
Biological species | Oryctolagus cuniculus (rabbit) / Homo sapiens (human) / Saccharomyces cerevisiae (brewer's yeast) / Canis lupus familiaris (dog) / Rabbit (rabbit) / Dog (dog) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Shanmuganathan V / Cheng J / Braunger K / Berninghausen O / Beatrix B / Beckmann R | |||||||||
Funding support | Germany, 1 items
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Citation | Journal: Elife / Year: 2019 Title: Structural and mutational analysis of the ribosome-arresting human XBP1u. Authors: Vivekanandan Shanmuganathan / Nina Schiller / Anastasia Magoulopoulou / Jingdong Cheng / Katharina Braunger / Florian Cymer / Otto Berninghausen / Birgitta Beatrix / Kenji Kohno / Gunnar von ...Authors: Vivekanandan Shanmuganathan / Nina Schiller / Anastasia Magoulopoulou / Jingdong Cheng / Katharina Braunger / Florian Cymer / Otto Berninghausen / Birgitta Beatrix / Kenji Kohno / Gunnar von Heijne / Roland Beckmann / Abstract: 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. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4745.map.gz | 23.6 MB | EMDB map data format | |
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Header (meta data) | emd-4745-v30.xml emd-4745.xml | 105.6 KB 105.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_4745_fsc.xml | 16 KB | Display | FSC data file |
Images | emd_4745.png | 220.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4745 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4745 | HTTPS FTP |
-Related structure data
Related structure data | 6r7qMC 4729C 4735C 4737C 6r5qC 6r6gC 6r6pC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_4745.map.gz / Format: CCP4 / Size: 236.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Structure of XBP1u-paused ribosome nascent chain complex with Sec61. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.084 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
+Entire : Structure of XBP1u-paused ribosome nascent chain complex with Sec61.
+Supramolecule #1: Structure of XBP1u-paused ribosome nascent chain complex with Sec61.
+Supramolecule #2: Ribosome
+Supramolecule #3: X-box-binding protein 1
+Supramolecule #4: tRNA
+Supramolecule #5: Sec61
+Supramolecule #6: mRNA
+Macromolecule #1: 40S ribosomal protein S30
+Macromolecule #2: 40S ribosomal protein S7
+Macromolecule #3: 40S ribosomal protein S8
+Macromolecule #4: Ribosomal protein S9 (Predicted)
+Macromolecule #5: Ribosomal protein S11
+Macromolecule #6: Ribosomal protein S28
+Macromolecule #7: uS10
+Macromolecule #8: eS21
+Macromolecule #9: uS13
+Macromolecule #10: 40S ribosomal protein S27
+Macromolecule #11: eS17
+Macromolecule #12: eS26
+Macromolecule #13: uS11
+Macromolecule #14: eS31
+Macromolecule #15: X-box-binding protein 1
+Macromolecule #20: ribosomal protein RACK1
+Macromolecule #23: uS14
+Macromolecule #24: eS24
+Macromolecule #25: ribosomal protein eS25
+Macromolecule #26: eS19
+Macromolecule #27: ribosomal protein uS15
+Macromolecule #28: 40S ribosomal protein S12
+Macromolecule #29: uL2
+Macromolecule #30: uL3
+Macromolecule #31: uL4
+Macromolecule #32: 60S ribosomal protein L5
+Macromolecule #33: 60S ribosomal protein L6
+Macromolecule #34: uL30
+Macromolecule #35: eL8
+Macromolecule #36: uL6
+Macromolecule #37: Ribosomal protein L10 (Predicted)
+Macromolecule #38: Ribosomal protein L11
+Macromolecule #40: 60S ribosomal protein L13
+Macromolecule #41: Ribosomal protein L14
+Macromolecule #42: Ribosomal protein L15
+Macromolecule #43: uL13
+Macromolecule #44: uL22
+Macromolecule #45: eL18
+Macromolecule #46: eL19
+Macromolecule #47: eL20
+Macromolecule #48: eL21
+Macromolecule #49: eL22
+Macromolecule #50: eL14
+Macromolecule #51: Ribosomal protein L24
+Macromolecule #52: uL23
+Macromolecule #53: Ribosomal protein L26
+Macromolecule #54: 60S ribosomal protein L27
+Macromolecule #55: eS10
+Macromolecule #56: uL15
+Macromolecule #57: eL29
+Macromolecule #58: eL30
+Macromolecule #59: eL31
+Macromolecule #60: eL32
+Macromolecule #61: eL33
+Macromolecule #62: eL34
+Macromolecule #63: uL29
+Macromolecule #64: 60S ribosomal protein L36
+Macromolecule #65: Ribosomal protein L37
+Macromolecule #66: eL38
+Macromolecule #67: eL39
+Macromolecule #68: eL40
+Macromolecule #69: 60s ribosomal protein l41
+Macromolecule #70: eL42
+Macromolecule #71: ribosomal protein eL43
+Macromolecule #72: uS2
+Macromolecule #73: eL28
+Macromolecule #74: 60S acidic ribosomal protein P0
+Macromolecule #75: uL11
+Macromolecule #76: 40S ribosomal protein S3a
+Macromolecule #77: uS5
+Macromolecule #78: Ribosomal protein S3
+Macromolecule #79: 40S ribosomal protein S4
+Macromolecule #80: Ribosomal protein S5
+Macromolecule #81: 40S ribosomal protein S6
+Macromolecule #82: Ribosomal protein S15a
+Macromolecule #83: Ribosomal protein S16
+Macromolecule #84: Ribosomal protein S23
+Macromolecule #85: uS19
+Macromolecule #86: Protein transport protein Sec61 subunit alpha isoform 1
+Macromolecule #87: Protein transport protein Sec61 subunit gamma
+Macromolecule #88: Protein transport protein Sec61 subunit beta
+Macromolecule #16: P-tRNA
+Macromolecule #17: E-tRNA
+Macromolecule #18: messenger RNA
+Macromolecule #19: 28S ribosomal RNA
+Macromolecule #21: 5S ribosomal RNA
+Macromolecule #22: 5.8S ribosomal RNA
+Macromolecule #39: 18S ribosomal RNA
+Macromolecule #89: ZINC ION
+Macromolecule #90: MAGNESIUM ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: FEI FALCON II (4k x 4k) / Average electron dose: 28.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Refinement | Protocol: RIGID BODY FIT |
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Output model | PDB-6r7q: |