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- PDB-6r6g: Structure of XBP1u-paused ribosome nascent chain complex with SRP. -
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Open data
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Basic information
Entry | Database: PDB / ID: 6r6g | ||||||
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Title | Structure of XBP1u-paused ribosome nascent chain complex with SRP. | ||||||
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![]() | RIBOSOME / translational pausing / XBP1 / UPR / cotranslational targeting / SRP. | ||||||
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 / positive regulation of plasma cell differentiation / signal recognition particle, endoplasmic reticulum targeting / positive regulation of lactation ...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 / positive regulation of plasma cell differentiation / signal recognition particle, endoplasmic reticulum targeting / positive regulation of lactation / sterol homeostasis / IRE1alpha activates chaperones / ATF6 (ATF6-alpha) activates chaperone genes / granulocyte differentiation / positive regulation of ERAD pathway / positive regulation of phospholipid biosynthetic process / signal recognition particle binding / negative regulation of myotube differentiation / intracellular triglyceride homeostasis / endoplasmic reticulum signal peptide binding / negative regulation of translational elongation / signal-recognition-particle GTPase / 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 / SRP-dependent cotranslational protein targeting to membrane / negative regulation of endoplasmic reticulum unfolded protein response / 7S RNA binding / exocrine pancreas development / 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 / SRP-dependent cotranslational protein targeting to membrane, translocation / 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 / neutrophil chemotaxis / liver development / maturation of LSU-rRNA / ribosomal large subunit biogenesis / cellular response to leukemia inhibitory factor Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / 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. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 4.9 MB | Display | ![]() |
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-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.6 MB | Display | |
Data in XML | ![]() | 373.5 KB | Display | |
Data in CIF | ![]() | 638.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4735MC ![]() 4729C ![]() 4737C ![]() 4745C ![]() 6r5qC ![]() 6r6pC ![]() 6r7qC C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
+Protein , 33 types, 33 molecules 09ABCFGHIIKKPPPQSSSTVWWXabcdefghoqr...
-Protein/peptide , 3 types, 3 molecules 1lAG
#2: Protein/peptide | Mass: 2895.380 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#71: Protein/peptide | Mass: 6324.579 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#92: Protein/peptide | Mass: 1375.909 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-RNA chain , 8 types, 8 molecules 234578KAF
#3: RNA chain | Mass: 24108.330 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#4: RNA chain | Mass: 24148.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#5: RNA chain | Mass: 1877.157 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
#6: RNA chain | Mass: 1148420.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#8: RNA chain | Mass: 38691.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#9: RNA chain | Mass: 48545.672 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#31: RNA chain | Mass: 548040.188 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#87: RNA chain | Mass: 66779.688 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Ribosomal protein ... , 20 types, 20 molecules 6DDEEFFGGIJMNOOQQTTUUVVWYjpwy
#7: Protein | Mass: 34669.113 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#17: Protein | Mass: 21649.633 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#19: Protein | Mass: 17586.766 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#21: Protein | Mass: 7007.069 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#23: Protein | Mass: 11395.489 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#27: Protein | Mass: 24511.861 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#30: Protein | Mass: 19399.498 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#35: Protein | Mass: 16217.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#37: Protein | Mass: 24076.088 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#40: Protein | Mass: 8526.119 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#44: Protein | Mass: 17057.113 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#50: Protein | Mass: 14734.357 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#51: Protein | Mass: 16032.804 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#53: Protein | Mass: 15626.392 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#55: Protein | Mass: 14131.536 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#58: Protein | Mass: 15891.787 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#69: Protein | Mass: 10090.891 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#75: Protein | Mass: 10168.153 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#82: Protein | Mass: 25215.586 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#84: Protein | Mass: 21525.941 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-40S ribosomal protein ... , 12 types, 12 molecules AABBCCHHJJLLMMNNRRuxz
#12: Protein | Mass: 6317.539 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#14: Protein | Mass: 21629.309 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#16: Protein | Mass: 24003.012 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#26: Protein | Mass: 9124.389 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#29: Protein | Mass: 9348.990 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#34: Protein | Mass: 11645.794 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#36: Protein | Mass: 14544.659 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#38: Protein | Mass: 14432.125 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#46: Protein | Mass: 13048.244 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#80: Protein | Mass: 24759.145 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#83: Protein | Mass: 29523.674 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#85: Protein | Mass: 27471.535 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-60S ribosomal protein ... , 11 types, 11 molecules DELORUZikmn
#18: Protein | Mass: 34077.391 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#20: Protein | Mass: 28818.293 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#33: Protein | Mass: 24200.525 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#39: Protein | Mass: 23144.859 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#45: Protein | Mass: 21613.033 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#52: Protein | Mass: 11495.275 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#59: Protein | Mass: 15704.635 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#68: Protein | Mass: 11888.371 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#70: Protein | Mass: 8107.752 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#72: Protein | Mass: 6199.574 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#73: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Signal recognition particle ... , 5 types, 5 molecules ABACAIADAE
#86: Protein | Mass: 47844.172 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#88: Protein | Mass: 12159.153 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#89: Protein | Mass: 23220.695 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#90: Protein | Mass: 8705.137 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#91: Protein | Mass: 10651.371 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Non-polymers , 2 types, 304 molecules ![](data/chem/img/MG.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/ZN.gif)
#93: Chemical | ChemComp-MG / #94: Chemical | ChemComp-ZN / |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 28 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
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Processing
EM software |
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CTF correction | Type: NONE | |||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||
3D reconstruction | Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 24875 / Symmetry type: POINT | |||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT |