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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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Keywords | translational pausing / XBP1 / UPR / RIBOSOME | |||||||||
Function / homology | Function and homology information ATF6-mediated unfolded protein response / organelle organization / positive regulation of protein acetylation / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / membrane docking / positive regulation of vascular wound healing / response to insulin-like growth factor stimulus / sterol homeostasis / positive regulation of lactation / IRE1alpha activates chaperones ...ATF6-mediated unfolded protein response / organelle organization / positive regulation of protein acetylation / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / membrane docking / positive regulation of vascular wound healing / response to insulin-like growth factor stimulus / sterol homeostasis / positive regulation of lactation / IRE1alpha activates chaperones / ATF6 (ATF6-alpha) activates chaperone genes / positive regulation of plasma cell differentiation / endoplasmic reticulum Sec complex / 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-transporting ATPase activity / cellular response to fructose stimulus / protein insertion into ER membrane / XBP1(S) activates chaperone genes / cellular response to laminar fluid shear stress / cellular response to nutrient / SRP-dependent cotranslational protein targeting to membrane, translocation / negative regulation of endoplasmic reticulum unfolded protein response / positive regulation of endothelial cell apoptotic process / positive regulation of endoplasmic reticulum unfolded protein response / cellular response to fluid shear stress / positive regulation of MHC class II biosynthetic process / signal sequence binding / post-translational protein targeting to membrane, translocation / positive regulation of vascular associated smooth muscle cell migration / positive regulation of hepatocyte proliferation / endothelial cell proliferation / cellular response to peptide hormone stimulus / muscle organ development / positive regulation of T cell differentiation / regulation of G1 to G0 transition / exit from mitosis / 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 / positive regulation of immunoglobulin production / protein-DNA complex disassembly / 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 / retinal ganglion cell axon guidance / mammalian oogenesis stage / G1 to G0 transition / negative regulation of SMAD protein signal transduction / activation-induced cell death of T cells / IRE1-mediated unfolded protein response / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / protein transmembrane transporter activity / neuron development / positive regulation of TOR signaling / 90S preribosome / cellular response to vascular endothelial growth factor stimulus / TOR signaling / positive regulation of fat cell differentiation / T cell proliferation involved in immune response / fatty acid homeostasis / adipose tissue development / cellular response to interleukin-4 / cis-regulatory region sequence-specific DNA binding / vascular endothelial growth factor receptor signaling pathway / erythrocyte development / cellular response to glucose starvation / cellular response to actinomycin D / negative regulation of ubiquitin-dependent protein catabolic process / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / positive regulation of autophagy / ribosomal small subunit export from nucleus / translation regulator activity / ERAD pathway / rough endoplasmic reticulum / endoplasmic reticulum unfolded protein response / positive regulation of vascular associated smooth muscle cell proliferation / gastrulation / MDM2/MDM4 family protein binding / maturation of LSU-rRNA / cytosolic ribosome / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / response to endoplasmic reticulum stress / phosphatidylinositol 3-kinase/protein kinase B signal transduction / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / rescue of stalled ribosome / ribosomal large subunit biogenesis / liver development / guanyl-nucleotide exchange factor activity / cholesterol homeostasis Similarity search - Function | |||||||||
Biological species | Oryctolagus cuniculus (rabbit) / Homo sapiens (human) / Saccharomyces cerevisiae (brewer's yeast) / Canis lupus familiaris (dog) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Shanmuganathan V / Cheng J | |||||||||
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 | 111.9 KB 111.9 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 | ||
Filedesc metadata | emd-4745.cif.gz | 20 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4745 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4745 | HTTPS FTP |
-Validation report
Summary document | emd_4745_validation.pdf.gz | 293.8 KB | Display | EMDB validaton report |
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Full document | emd_4745_full_validation.pdf.gz | 293 KB | Display | |
Data in XML | emd_4745_validation.xml.gz | 14.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4745 ftp://ftp.pdbj.org/pub/emdb/validation_reports/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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
-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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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 |
+Image processing
-Atomic model buiding 1
Refinement | Protocol: RIGID BODY FIT |
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Output model | PDB-6r7q: |