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- 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. | |||||||||
![]() | Structure of XBP1u-paused nascent chain complex with SRP. | |||||||||
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Function / homology | ![]() ATF6-mediated unfolded protein response / SRP-dependent cotranslational protein targeting to membrane / organelle organization / positive regulation of protein acetylation / SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition / response to insulin-like growth factor stimulus / positive regulation of vascular wound healing / signal recognition particle, endoplasmic reticulum targeting / positive regulation of lactation / sterol homeostasis ...ATF6-mediated unfolded protein response / SRP-dependent cotranslational protein targeting to membrane / organelle organization / positive regulation of protein acetylation / SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition / response to insulin-like growth factor stimulus / positive regulation of vascular wound healing / signal recognition particle, endoplasmic reticulum targeting / positive regulation of lactation / sterol homeostasis / IRE1alpha activates chaperones / positive regulation of plasma cell differentiation / ATF6 (ATF6-alpha) activates chaperone genes / endoplasmic reticulum signal peptide binding / granulocyte differentiation / positive regulation of ERAD pathway / positive regulation of phospholipid biosynthetic process / negative regulation of myotube differentiation / signal recognition particle binding / intracellular triglyceride homeostasis / signal-recognition-particle GTPase / negative regulation of translational elongation / protein targeting to ER / cellular response to fructose stimulus / XBP1(S) activates chaperone genes / cellular response to laminar fluid shear stress / cellular response to nutrient / 7S RNA binding / exocrine pancreas development / negative regulation of endoplasmic reticulum unfolded protein response / positive regulation of endothelial cell apoptotic process / SRP-dependent cotranslational protein targeting to membrane / SRP-dependent cotranslational protein targeting to membrane, translocation / 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 / cellular response to peptide hormone stimulus / regulation of G1 to G0 transition / muscle organ development / positive regulation of T cell differentiation / exit from mitosis / positive regulation of immunoglobulin production / 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 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 / phagocytic cup / ubiquitin ligase inhibitor activity / TOR signaling / positive regulation of TOR signaling / 90S preribosome / cellular response to vascular endothelial growth factor stimulus / neuron development / positive regulation of fat cell differentiation / T cell proliferation involved in immune response / fatty acid homeostasis / cellular response to interleukin-4 / cis-regulatory region sequence-specific DNA binding / adipose tissue development / erythrocyte development / vascular endothelial growth factor receptor signaling pathway / negative regulation of ubiquitin-dependent protein catabolic process / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / translation regulator activity / cellular response to actinomycin D / positive regulation of autophagy / ribosomal small subunit export from nucleus / cellular response to glucose starvation / ERAD pathway / cytosolic ribosome / endoplasmic reticulum unfolded protein response / rough endoplasmic reticulum / 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 / neutrophil chemotaxis / phosphatidylinositol 3-kinase/protein kinase B signal transduction / maturation of LSU-rRNA / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / response to endoplasmic reticulum stress / rescue of stalled ribosome / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of apoptotic signaling pathway / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / liver development / ribosomal large subunit biogenesis Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
![]() | Shanmuganathan V / Cheng J / Braunger K / Berninghausen O / Beatrix B / Beckmann R | |||||||||
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
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 28.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 114.4 KB 114.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 16 KB | Display | ![]() |
Images | ![]() | 189.4 KB | ||
Others | ![]() | 222.1 MB | ||
Archive directory | ![]() ![]() | 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 | ![]() ![]() |
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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 nascent chain complex with SRP. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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![]() | 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-6r6g: |