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- EMDB-4737: Structure of XBP1u-paused ribosome nascent chain complex (rotated... -
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Basic information
Entry | Database: EMDB / ID: EMD-4737 | |||||||||
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Title | Structure of XBP1u-paused ribosome nascent chain complex (rotated state) | |||||||||
![]() | Structure of XBP1u-paused ribosome nascent chain complex (rotated state) | |||||||||
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![]() | translational pausing / XBP1 / UPR / RIBOSOME | |||||||||
Function / homology | ![]() ATF6-mediated unfolded protein response / organelle organization / positive regulation of protein acetylation / response to insulin-like growth factor stimulus / positive regulation of vascular wound healing / positive regulation of plasma cell differentiation / positive regulation of lactation / sterol homeostasis / IRE1alpha activates chaperones / ATF6 (ATF6-alpha) activates chaperone genes ...ATF6-mediated unfolded protein response / organelle organization / positive regulation of protein acetylation / response to insulin-like growth factor stimulus / positive regulation of vascular wound healing / positive regulation of plasma cell differentiation / positive regulation of lactation / sterol homeostasis / IRE1alpha activates chaperones / ATF6 (ATF6-alpha) activates chaperone genes / positive regulation of ERAD pathway / positive regulation of phospholipid biosynthetic process / negative regulation of myotube differentiation / intracellular triglyceride homeostasis / cellular response to fructose stimulus / XBP1(S) activates chaperone genes / cellular response to laminar fluid shear stress / cellular response to nutrient / negative regulation of endoplasmic reticulum unfolded protein response / 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 / positive regulation of hepatocyte proliferation / endothelial cell proliferation / positive regulation of T cell differentiation / cellular response to peptide hormone stimulus / regulation of G1 to G0 transition / exit from mitosis / muscle organ development / 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 / protein-DNA complex disassembly / positive regulation of immunoglobulin production / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / optic nerve development / positive regulation of B cell differentiation / mammalian oogenesis stage / retinal ganglion cell axon guidance / G1 to G0 transition / activation-induced cell death of T cells / 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 / phagocytic cup / positive regulation of TOR signaling / TOR signaling / neuron development / T cell proliferation involved in immune response / cellular response to vascular endothelial growth factor stimulus / positive regulation of fat cell differentiation / fatty acid homeostasis / cellular response to interleukin-4 / ribosomal small subunit export from nucleus / cis-regulatory region sequence-specific DNA binding / erythrocyte development / adipose tissue development / translation regulator activity / cellular response to glucose starvation / vascular endothelial growth factor receptor signaling pathway / cellular response to actinomycin D / positive regulation of autophagy / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / cytosolic ribosome / ERAD pathway / rough endoplasmic reticulum / endoplasmic reticulum unfolded protein response / gastrulation / MDM2/MDM4 family protein binding / positive regulation of vascular associated smooth muscle cell proliferation / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / negative regulation of ubiquitin-dependent protein catabolic process / rescue of stalled ribosome / response to endoplasmic reticulum stress / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / 90S preribosome / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / phosphatidylinositol 3-kinase/protein kinase B signal transduction / liver development / maturation of LSU-rRNA / ribosomal large subunit biogenesis / cellular response to leukemia inhibitory factor / maturation of SSU-rRNA / positive regulation of translation / cholesterol homeostasis / regulation of cell growth / nuclear estrogen receptor binding / cellular response to glucose stimulus / small-subunit processome / positive regulation of apoptotic signaling pathway / protein kinase C binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / cellular response to amino acid stimulus / negative regulation of transforming growth factor beta receptor signaling pathway / protein destabilization / positive regulation of protein-containing complex assembly Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
![]() | Shanmuganathan V / Cheng J | |||||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 24.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 109.8 KB 109.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.1 KB | Display | ![]() |
Images | ![]() | 232.3 KB | ||
Filedesc metadata | ![]() | 19.4 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 285.9 KB | Display | ![]() |
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Full document | ![]() | 285 KB | Display | |
Data in XML | ![]() | 13.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6r6pMC ![]() 4729C ![]() 4735C ![]() 4745C ![]() 6r5qC ![]() 6r6gC ![]() 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 | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Structure of XBP1u-paused ribosome nascent chain complex (rotated state) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
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Sample components
+Entire : Structure of XBP1u-paused ribosome nascent chain complex (rotated...
+Supramolecule #1: Structure of XBP1u-paused ribosome nascent chain complex (rotated...
+Supramolecule #2: Structure of XBP1u-paused ribosome nascent chain complex (rotated...
+Supramolecule #3: A/P- and P/E- site tRNA
+Supramolecule #4: X-box-binding protein 1
+Supramolecule #5: mRNA
+Macromolecule #1: 28S ribosomal RNA
+Macromolecule #2: 5S ribosomal RNA
+Macromolecule #3: 5.8S ribosomal RNA
+Macromolecule #49: A/P-tRNA
+Macromolecule #50: P/E-tRNA
+Macromolecule #51: 18S rRNA
+Macromolecule #85: mRNA
+Macromolecule #4: uL2
+Macromolecule #5: uL3
+Macromolecule #6: uL4
+Macromolecule #7: 60S ribosomal protein L5
+Macromolecule #8: 60S ribosomal protein L6
+Macromolecule #9: uL30
+Macromolecule #10: eL8
+Macromolecule #11: uL6
+Macromolecule #12: Ribosomal protein L10 (Predicted)
+Macromolecule #13: uL5
+Macromolecule #14: 60S ribosomal protein L13
+Macromolecule #15: Ribosomal protein L14
+Macromolecule #16: Ribosomal protein L15
+Macromolecule #17: uL13
+Macromolecule #18: uL22
+Macromolecule #19: eL18
+Macromolecule #20: eL19
+Macromolecule #21: eL20
+Macromolecule #22: eL21
+Macromolecule #23: Ribosomal protein L22
+Macromolecule #24: uL14
+Macromolecule #25: Ribosomal protein L24
+Macromolecule #26: uL23
+Macromolecule #27: Ribosomal protein L26
+Macromolecule #28: 60S ribosomal protein L27
+Macromolecule #29: uL15
+Macromolecule #30: 60S ribosomal protein L29
+Macromolecule #31: eL30
+Macromolecule #32: eL31
+Macromolecule #33: eL32
+Macromolecule #34: eL33
+Macromolecule #35: eL34
+Macromolecule #36: uL29
+Macromolecule #37: 60S ribosomal protein L36
+Macromolecule #38: Ribosomal protein L37
+Macromolecule #39: eL38
+Macromolecule #40: ribosomal protein eL39
+Macromolecule #41: eL40
+Macromolecule #42: 60s ribosomal protein l41
+Macromolecule #43: eL42
+Macromolecule #44: ribosomal protein eL43
+Macromolecule #45: eL28
+Macromolecule #46: 60S acidic ribosomal protein P0
+Macromolecule #47: Ribosomal protein L12
+Macromolecule #48: X-box-binding protein 1
+Macromolecule #52: uS2
+Macromolecule #53: 40S ribosomal protein S3a
+Macromolecule #54: uS5
+Macromolecule #55: 40S ribosomal protein S4
+Macromolecule #56: 40S ribosomal protein S6
+Macromolecule #57: 40S ribosomal protein S7
+Macromolecule #58: 40S ribosomal protein S8
+Macromolecule #59: Ribosomal protein S9 (Predicted)
+Macromolecule #60: Ribosomal protein S11
+Macromolecule #61: ribosomal protein uS15
+Macromolecule #62: uS11
+Macromolecule #63: Ribosomal protein S16
+Macromolecule #64: eS17
+Macromolecule #65: eS21
+Macromolecule #66: Ribosomal protein S15a
+Macromolecule #67: Ribosomal protein S23
+Macromolecule #68: eS24
+Macromolecule #69: eS26
+Macromolecule #70: 40S ribosomal protein S27
+Macromolecule #71: 40S ribosomal protein S30
+Macromolecule #72: Ribosomal protein S3
+Macromolecule #73: Ribosomal protein S5
+Macromolecule #74: eS10
+Macromolecule #75: 40S ribosomal protein S12
+Macromolecule #76: uS14
+Macromolecule #77: uS13
+Macromolecule #78: eS19
+Macromolecule #79: uS10
+Macromolecule #80: ribosomal protein eS25
+Macromolecule #81: Ribosomal protein S28
+Macromolecule #82: S29
+Macromolecule #83: eS31
+Macromolecule #84: ribosomal protein RACK1
+Macromolecule #86: MAGNESIUM ION
+Macromolecule #87: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | 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: ![]() |
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-6r6p: |