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Yorodumi- PDB-6r6g: Structure of XBP1u-paused ribosome nascent chain complex with SRP. -
+Open data
-Basic information
Entry | Database: PDB / ID: 6r6g | ||||||
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Title | Structure of XBP1u-paused ribosome nascent chain complex with SRP. | ||||||
Components |
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Keywords | RIBOSOME / translational pausing / XBP1 / UPR / cotranslational targeting / SRP. | ||||||
Function / homology | Function and homology information 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 / negative regulation of SMAD protein signal transduction / XBP1(S) activates chaperone genes / cellular response to laminar fluid shear stress / 7S RNA binding / cellular response to nutrient / 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, translocation / SRP-dependent cotranslational protein targeting to membrane / 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 / positive regulation of fat cell differentiation / retinal ganglion cell axon guidance / mammalian oogenesis stage / G1 to G0 transition / 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 / 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 / cellular response to amino acid stimulus / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / negative regulation of transforming growth factor beta receptor signaling pathway / positive regulation of apoptotic signaling pathway / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Oryctolagus cuniculus (rabbit) Saccharomyces cerevisiae (brewer's yeast) Canis lupus familiaris (dog) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | ||||||
Authors | Shanmuganathan, V. / Cheng, J. / Braunger, K. / Berninghausen, O. / Beatrix, B. / Beckmann, R. | ||||||
Funding support | Germany, 1items
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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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6r6g.cif.gz | 4.9 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6r6g.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6r6g.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6r6g_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 6r6g_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 6r6g_validation.xml.gz | 373.5 KB | Display | |
Data in CIF | 6r6g_validation.cif.gz | 638.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/r6/6r6g ftp://data.pdbj.org/pub/pdb/validation_reports/r6/6r6g | HTTPS FTP |
-Related structure data
Related structure data | 4735MC 4729C 4737C 4745C 6r5qC 6r6pC 6r7qC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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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.) Homo sapiens (human) / Gene: XBP1, TREB5, XBP2 / Production host: Oryctolagus cuniculus (rabbit) / References: UniProt: P17861 |
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#71: Protein/peptide | Mass: 6324.579 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TTN1 |
#92: Protein/peptide | Mass: 1375.909 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
-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) Saccharomyces cerevisiae (brewer's yeast) |
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#4: RNA chain | Mass: 24148.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Saccharomyces cerevisiae (brewer's yeast) |
#5: RNA chain | Mass: 1877.157 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) |
#6: RNA chain | Mass: 1148420.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#8: RNA chain | Mass: 38691.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#9: RNA chain | Mass: 48545.672 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#31: RNA chain | Mass: 548040.188 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#87: RNA chain | Mass: 66779.688 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Canis lupus familiaris (dog) |
-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) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SJB4 |
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#17: Protein | Mass: 21649.633 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: B7NZS8 |
#19: Protein | Mass: 17586.766 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TRM4 |
#21: Protein | Mass: 7007.069 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TIB4 |
#23: Protein | Mass: 11395.489 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#27: Protein | Mass: 24511.861 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: B7NZQ2 |
#30: Protein | Mass: 19399.498 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TUB8 |
#35: Protein | Mass: 16217.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: U3KNW6 |
#37: Protein | Mass: 24076.088 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1T0C1 |
#40: Protein | Mass: 8526.119 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TDB3 |
#44: Protein | Mass: 17057.113 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SP51 |
#50: Protein | Mass: 14734.357 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TG89 |
#51: Protein | Mass: 16032.804 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SGX4 |
#53: Protein | Mass: 15626.392 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SZ47 |
#55: Protein | Mass: 14131.536 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SE28 |
#58: Protein | Mass: 15891.787 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SQH0 |
#69: Protein | Mass: 10090.891 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: U3KPD5 |
#75: Protein | Mass: 10168.153 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SY53 |
#82: Protein | Mass: 25215.586 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TNM3 |
#84: Protein | Mass: 21525.941 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TFM5 |
-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) Oryctolagus cuniculus (rabbit) / References: UniProt: G1T8A2 |
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#14: Protein | Mass: 21629.309 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SVB0 |
#16: Protein | Mass: 24003.012 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TJW1 |
#26: Protein | Mass: 9124.389 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#29: Protein | Mass: 9348.990 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TZ76 |
#34: Protein | Mass: 11645.794 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#36: Protein | Mass: 14544.659 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#38: Protein | Mass: 14432.125 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#46: Protein | Mass: 13048.244 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SFR8 |
#80: Protein | Mass: 24759.145 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SS70 |
#83: Protein | Mass: 29523.674 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TK17 |
#85: Protein | Mass: 27471.535 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TM55 |
-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) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SYJ6 |
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#20: Protein | Mass: 28818.293 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SKF7 |
#33: Protein | Mass: 24200.525 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TPV0 |
#39: Protein | Mass: 23144.859 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#45: Protein | Mass: 21613.033 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#52: Protein | Mass: 11495.275 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#59: Protein | Mass: 15704.635 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TXF6 |
#68: Protein | Mass: 11888.371 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TTQ5 |
#70: Protein | Mass: 8107.752 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#72: Protein | Mass: 6199.574 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#73: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: A0A087WNH4 |
-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) Canis lupus familiaris (dog) / References: UniProt: P61010 |
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#88: Protein | Mass: 12159.153 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Canis lupus familiaris (dog) / References: UniProt: J9PAS6 |
#89: Protein | Mass: 23220.695 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Canis lupus familiaris (dog) / References: UniProt: Q00004 |
#90: Protein | Mass: 8705.137 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Canis lupus familiaris (dog) / References: UniProt: F1Q0Z5 |
#91: Protein | Mass: 10651.371 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Canis lupus familiaris (dog) / References: UniProt: P16255 |
-Non-polymers , 2 types, 304 molecules
#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 |
-Sample preparation
Component |
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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 |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 28 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
-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 |