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Yorodumi- EMDB-4735: Structure of XBP1u-paused ribosome nascent chain complex with SRP. -
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Open data
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Basic information
| Entry | Database: EMDB / ID: EMD-4735 | |||||||||
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| Title | Structure of XBP1u-paused ribosome nascent chain complex with SRP. | |||||||||
Map data | Structure of XBP1u-paused nascent chain complex with SRP. | |||||||||
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Keywords | translational pausing / XBP1 / UPR / cotranslational targeting / SRP. / RIBOSOME | |||||||||
| Function / homology | Function and homology informationSRP-dependent cotranslational protein targeting to membrane / positive regulation of vascular wound healing / positive regulation of protein acetylation / ATF6-mediated unfolded protein response / endoplasmic reticulum signal sequence receptor activity / SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition / signal recognition particle, endoplasmic reticulum targeting / granulocyte differentiation / sterol homeostasis / IRE1alpha activates chaperones ...SRP-dependent cotranslational protein targeting to membrane / positive regulation of vascular wound healing / positive regulation of protein acetylation / ATF6-mediated unfolded protein response / endoplasmic reticulum signal sequence receptor activity / SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition / signal recognition particle, endoplasmic reticulum targeting / granulocyte differentiation / sterol homeostasis / IRE1alpha activates chaperones / ATF6 (ATF6-alpha) activates chaperone genes / positive regulation of plasma cell differentiation / positive regulation of phospholipid biosynthetic process / negative regulation of myotube differentiation / positive regulation of ERAD pathway / intracellular triglyceride homeostasis / signal recognition particle binding / signal-recognition-particle GTPase / negative regulation of translational elongation / positive regulation of hepatocyte proliferation / cellular response to fructose stimulus / positive regulation of lactation / exocrine pancreas development / cellular response to fluid shear stress / protein targeting to ER / cellular response to laminar fluid shear stress / SRP-dependent cotranslational protein targeting to membrane, translocation / 7S RNA binding / XBP1(S) activates chaperone genes / endothelial cell proliferation / cellular response to nutrient / positive regulation of MHC class II biosynthetic process / SRP-dependent cotranslational protein targeting to membrane / positive regulation of vascular associated smooth muscle cell migration / negative regulation of endoplasmic reticulum unfolded protein response / positive regulation of cytokine production involved in inflammatory response / cellular response to peptide hormone stimulus / positive regulation of B cell differentiation / muscle organ development / positive regulation of T cell differentiation / positive regulation of immunoglobulin production / IRE1-mediated unfolded protein response / adipose tissue development / cellular response to interleukin-4 / negative regulation of SMAD protein signal transduction / cellular response to vascular endothelial growth factor stimulus / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / ubiquitin-like protein ligase binding / neuron development / positive regulation of endothelial cell apoptotic process / fatty acid homeostasis / positive regulation of fat cell differentiation / vascular endothelial growth factor receptor signaling pathway / positive regulation of TOR signaling / ribonucleoprotein complex binding / response to insulin-like growth factor stimulus / ubiquitin ligase inhibitor activity / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / 90S preribosome / positive regulation of signal transduction by p53 class mediator / cellular response to glucose starvation / positive regulation of vascular associated smooth muscle cell proliferation / cis-regulatory region sequence-specific DNA binding / neutrophil chemotaxis / phagocytic cup / gastrulation / endoplasmic reticulum unfolded protein response / ERAD pathway / cholesterol homeostasis / translation regulator activity / rough endoplasmic reticulum / ribosomal small subunit export from nucleus / MDM2/MDM4 family protein binding / liver development / positive regulation of autophagy / response to endoplasmic reticulum stress / positive regulation of apoptotic signaling pathway / nuclear estrogen receptor binding / DNA-(apurinic or apyrimidinic site) lyase / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / cellular response to amino acid stimulus / regulation of autophagy / phosphatidylinositol 3-kinase/protein kinase B signal transduction / ribosomal large subunit biogenesis / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / RNA polymerase II transcription regulatory region sequence-specific DNA binding / cytosolic ribosome / maturation of SSU-rRNA / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / cellular response to glucose stimulus / negative regulation of transforming growth factor beta receptor signaling pathway / regulation of protein stability / regulation of cell growth / small-subunit processome / negative regulation of ERK1 and ERK2 cascade / protein destabilization / chromatin DNA binding / positive regulation of protein import into nucleus / positive regulation of interleukin-6 production / positive regulation of protein phosphorylation Similarity search - Function | |||||||||
| Biological species | ![]() ![]() Homo sapiens (human) / ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
Authors | Shanmuganathan V / Cheng J | |||||||||
| Funding support | Germany, 1 items
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Citation | Journal: Elife / Year: 2019Title: 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 |
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| Structure viewer | EM map: SurfView Molmil Jmol/JSmol |
| Supplemental images |
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Downloads & links
-EMDB archive
| Map data | emd_4735.map.gz | 28.7 MB | EMDB map data format | |
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| Header (meta data) | emd-4735-v30.xml emd-4735.xml | 121.2 KB 121.2 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_4735_fsc.xml | 16 KB | Display | FSC data file |
| Images | emd_4735.png | 189.4 KB | ||
| Filedesc metadata | emd-4735.cif.gz | 20.6 KB | ||
| Others | emd_4735_additional.map.gz | 222.1 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4735 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4735 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 6r6gMC ![]() 4729C ![]() 4737C ![]() 4745C ![]() 6r5qC ![]() 6r6pC ![]() 6r7qC C: citing same article ( M: atomic model generated by this map |
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| Similar structure data |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_4735.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 nascent chain complex with SRP. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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
-Additional map: Structure of XBP1u-paused nascent chain complex with SRP...
| File | emd_4735_additional.map | ||||||||||||
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| Annotation | Structure of XBP1u-paused nascent chain complex with SRP (lowpass filtered at 6 A) | ||||||||||||
| Projections & Slices |
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| Density Histograms |
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Sample components
+Entire : Structure of XBP1u-paused ribosome nascent chain complex with SRP.
+Supramolecule #1: Structure of XBP1u-paused ribosome nascent chain complex with SRP.
+Supramolecule #2: Structure of XBP1u-paused nascent chain complex with SRP.
+Supramolecule #3: P- and E- site tRNA
+Supramolecule #4: X-box-binding protein 1
+Supramolecule #5: mRNA encoding XBP1u
+Supramolecule #6: SRP
+Supramolecule #7: Signal sequence (HR2)
+Macromolecule #1: eS31
+Macromolecule #2: X-box-binding protein 1
+Macromolecule #7: ribosomal protein RACK1
+Macromolecule #10: uS14
+Macromolecule #11: uL2
+Macromolecule #12: 40S ribosomal protein S30
+Macromolecule #13: uL3
+Macromolecule #14: 40S ribosomal protein S7
+Macromolecule #15: uL4
+Macromolecule #16: 40S ribosomal protein S8
+Macromolecule #17: Ribosomal protein S9 (Predicted)
+Macromolecule #18: 60S ribosomal protein L5
+Macromolecule #19: Ribosomal protein S11
+Macromolecule #20: 60S ribosomal protein L6
+Macromolecule #21: Ribosomal protein S28
+Macromolecule #22: uL30
+Macromolecule #23: Ribosomal protein S20
+Macromolecule #24: eL8
+Macromolecule #25: uL6
+Macromolecule #26: 40S ribosomal protein S21
+Macromolecule #27: Ribosomal protein L10 (Predicted)
+Macromolecule #28: uS13
+Macromolecule #29: 40S ribosomal protein S27
+Macromolecule #30: Ribosomal protein L11
+Macromolecule #32: eS17
+Macromolecule #33: 60S ribosomal protein L13
+Macromolecule #34: 40S ribosomal protein S26
+Macromolecule #35: Ribosomal protein L14
+Macromolecule #36: 40S ribosomal protein S14
+Macromolecule #37: Ribosomal protein L15
+Macromolecule #38: 40S ribosomal protein S24
+Macromolecule #39: 60S ribosomal protein L13a
+Macromolecule #40: ribosomal protein eS25
+Macromolecule #41: uL22
+Macromolecule #42: eS19
+Macromolecule #43: eL18
+Macromolecule #44: ribosomal protein uS15
+Macromolecule #45: 60S ribosomal protein L19
+Macromolecule #46: 40S ribosomal protein S12
+Macromolecule #47: eL20
+Macromolecule #48: eS10
+Macromolecule #49: eL21
+Macromolecule #50: Ribosomal protein S15a
+Macromolecule #51: Ribosomal protein S16
+Macromolecule #52: 60S ribosomal protein L22
+Macromolecule #53: Ribosomal protein S23
+Macromolecule #54: eL14
+Macromolecule #55: Ribosomal protein L24
+Macromolecule #56: uS19
+Macromolecule #57: uL23
+Macromolecule #58: Ribosomal protein L26
+Macromolecule #59: 60S ribosomal protein L27
+Macromolecule #60: uL15
+Macromolecule #61: eL29
+Macromolecule #62: eL30
+Macromolecule #63: eL31
+Macromolecule #64: eL32
+Macromolecule #65: eL33
+Macromolecule #66: eL34
+Macromolecule #67: uL29
+Macromolecule #68: 60S ribosomal protein L36
+Macromolecule #69: Ribosomal protein L37
+Macromolecule #70: 60S ribosomal protein L38
+Macromolecule #71: eL39
+Macromolecule #72: 60S ribosomal protein L40
+Macromolecule #73: 60s ribosomal protein l41
+Macromolecule #74: eL42
+Macromolecule #75: ribosomal protein eL43
+Macromolecule #76: uS2
+Macromolecule #77: eL28
+Macromolecule #78: 60S acidic ribosomal protein P0
+Macromolecule #79: uL11
+Macromolecule #80: 40S ribosomal protein S3a
+Macromolecule #81: uS5
+Macromolecule #82: Ribosomal protein S3
+Macromolecule #83: 40S ribosomal protein S4
+Macromolecule #84: Ribosomal protein S5
+Macromolecule #85: 40S ribosomal protein S6
+Macromolecule #86: Signal recognition particle 54 kDa protein
+Macromolecule #88: Signal recognition particle subunit SRP19
+Macromolecule #89: Signal recognition particle subunit SRP68
+Macromolecule #90: Signal recognition particle 9 kDa protein
+Macromolecule #91: Signal recognition particle 14 kDa protein
+Macromolecule #92: Signal sequence (HR2)
+Macromolecule #3: P-tRNA
+Macromolecule #4: E-tRNA
+Macromolecule #5: mRNA
+Macromolecule #6: 28S ribosomal RNA
+Macromolecule #8: 5S ribosomal RNA
+Macromolecule #9: 5.8S ribosomal RNA
+Macromolecule #31: 18S ribosomal RNA
+Macromolecule #87: 7S RNA
+Macromolecule #93: MAGNESIUM ION
+Macromolecule #94: ZINC ION
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.5 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | FEI TITAN KRIOS |
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| Image recording | Film or detector model: FEI FALCON II (4k x 4k) / Average electron dose: 28.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
| Refinement | Protocol: RIGID BODY FIT |
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| Output model | ![]() PDB-6r6g: |
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About Yorodumi


Keywords

Homo sapiens (human)
Authors
Germany, 1 items
Citation

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