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Yorodumi- PDB-6r7q: Structure of XBP1u-paused ribosome nascent chain complex with Sec61. -
+Open data
-Basic information
Entry | Database: PDB / ID: 6r7q | ||||||
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Title | Structure of XBP1u-paused ribosome nascent chain complex with Sec61. | ||||||
Components |
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Keywords | RIBOSOME / translational pausing / XBP1 / UPR | ||||||
Function / homology | Function and homology information ATF6-mediated unfolded protein response / positive regulation of protein acetylation / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / response to insulin-like growth factor stimulus / positive regulation of vascular wound healing / organelle organization / membrane docking / positive regulation of plasma cell differentiation / positive regulation of lactation / IRE1alpha activates chaperones ...ATF6-mediated unfolded protein response / positive regulation of protein acetylation / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / response to insulin-like growth factor stimulus / positive regulation of vascular wound healing / organelle organization / membrane docking / positive regulation of plasma cell differentiation / positive regulation of lactation / IRE1alpha activates chaperones / sterol homeostasis / ATF6 (ATF6-alpha) activates chaperone genes / positive regulation of ERAD pathway / endoplasmic reticulum Sec complex / pronephric nephron development / : / positive regulation of phospholipid biosynthetic process / 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 / negative regulation of endoplasmic reticulum unfolded protein response / cellular response to laminar fluid shear stress / cellular response to nutrient / SRP-dependent cotranslational protein targeting to membrane, translocation / cellular response to fluid shear stress / signal sequence binding / positive regulation of endothelial cell apoptotic process / positive regulation of MHC class II biosynthetic process / post-translational protein targeting to membrane, translocation / positive regulation of endoplasmic reticulum unfolded protein response / positive regulation of vascular associated smooth muscle cell migration / endothelial cell proliferation / positive regulation of hepatocyte proliferation / muscle organ development / ERAD pathway / positive regulation of T cell differentiation / cellular response to peptide hormone stimulus / positive regulation of B cell differentiation / IRE1-mediated unfolded protein response / protein transmembrane transporter activity / positive regulation of immunoglobulin production / neuron development / positive regulation of TOR signaling / positive regulation of fat cell differentiation / fatty acid homeostasis / cellular response to vascular endothelial growth factor stimulus / cellular response to glucose starvation / adipose tissue development / rough endoplasmic reticulum / cis-regulatory region sequence-specific DNA binding / vascular endothelial growth factor receptor signaling pathway / positive regulation of autophagy / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / endoplasmic reticulum unfolded protein response / positive regulation of vascular associated smooth muscle cell proliferation / cellular response to interleukin-4 / DNA-(apurinic or apyrimidinic site) lyase / response to endoplasmic reticulum stress / cytosolic ribosome / cholesterol homeostasis / liver development / phosphatidylinositol 3-kinase/protein kinase B signal transduction / nuclear estrogen receptor binding / regulation of cell growth / cellular response to glucose stimulus / cellular response to amino acid stimulus / phospholipid binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / negative regulation of transforming growth factor beta receptor signaling pathway / protein destabilization / regulation of protein stability / negative regulation of ERK1 and ERK2 cascade / chromatin DNA binding / autophagy / positive regulation of interleukin-6 production / positive regulation of protein import into nucleus / RNA polymerase II transcription regulator complex / cellular response to insulin stimulus / fatty acid biosynthetic process / positive regulation of angiogenesis / ribosome binding / sequence-specific double-stranded DNA binding / protein transport / ribosome biogenesis / cellular response to oxidative stress / 5S rRNA binding / ubiquitin-dependent protein catabolic process / angiogenesis / cellular response to lipopolysaccharide / protease binding / transcription by RNA polymerase II / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / transcription cis-regulatory region binding 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: 3.9 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
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PDBx/mmCIF format | 6r7q.cif.gz | 4.8 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6r7q.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6r7q.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/r7/6r7q ftp://data.pdbj.org/pub/pdb/validation_reports/r7/6r7q | HTTPS FTP |
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-Related structure data
Related structure data | 4745MC 4729C 4735C 4737C 6r5qC 6r6gC 6r6pC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-40S ribosomal protein ... , 8 types, 8 molecules AABBCCJJRRuxz
#1: 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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#2: Protein | Mass: 21629.309 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SVB0 |
#3: Protein | Mass: 24003.012 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TJW1 |
#10: Protein | Mass: 9348.990 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TZ76 |
#28: Protein | Mass: 13048.244 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SFR8 |
#76: Protein | Mass: 24759.145 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SS70 |
#79: Protein | Mass: 29523.674 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TK17 |
#81: Protein | Mass: 27471.535 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TM55 |
-Ribosomal protein ... , 19 types, 19 molecules DDEEFF6OOQQIJMNWYjpwyTTUUVV
#4: Protein | Mass: 21649.633 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: B7NZS8 |
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#5: Protein | Mass: 17586.766 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TRM4 |
#6: Protein | Mass: 7007.069 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TIB4 |
#20: Protein | Mass: 34669.113 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SJB4 |
#25: Protein | Mass: 8526.119 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TDB3 |
#27: Protein | Mass: 17057.113 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SP51 |
#37: Protein | Mass: 24511.861 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: B7NZQ2 |
#38: Protein | Mass: 19399.498 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TUB8 |
#41: Protein | Mass: 16217.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: U3KNW6 |
#42: Protein | Mass: 24076.088 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1T0C1 |
#51: Protein | Mass: 14131.536 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SE28 |
#53: Protein | Mass: 15891.787 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SQH0 |
#65: Protein | Mass: 10090.891 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: U3KPD5 |
#71: Protein | Mass: 10168.153 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SY53 |
#78: Protein | Mass: 25215.586 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TNM3 |
#80: Protein | Mass: 21525.941 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TFM5 |
#82: Protein | Mass: 14734.357 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TG89 |
#83: Protein | Mass: 16032.804 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SGX4 |
#84: Protein | Mass: 15626.392 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SZ47 |
+Protein , 43 types, 43 molecules GGHHIIKKLLMM09NNPPABCFGHOPQRSTUVXSSabcd...
-Protein/peptide , 2 types, 2 molecules 1l
#15: 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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#67: 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 |
-RNA chain , 7 types, 7 molecules 234578K
#16: 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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#17: RNA chain | Mass: 24148.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Saccharomyces cerevisiae (brewer's yeast) |
#18: RNA chain | Mass: 1877.157 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) |
#19: RNA chain | Mass: 1148460.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#21: RNA chain | Mass: 38691.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#22: RNA chain | Mass: 48545.672 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
#39: RNA chain | Mass: 548040.188 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) |
-60S ribosomal protein ... , 6 types, 6 molecules DELZin
#32: 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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#33: Protein | Mass: 28818.293 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1SKF7 |
#40: Protein | Mass: 24200.525 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TPV0 |
#54: Protein | Mass: 15704.635 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TXF6 |
#64: Protein | Mass: 11888.371 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: G1TTQ5 |
#69: 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 |
-Protein transport protein Sec61 subunit ... , 3 types, 3 molecules XXYYZZ
#86: Protein | Mass: 50728.480 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Canis lupus familiaris (dog) / References: UniProt: P38377 |
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#87: Protein | Mass: 7019.456 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Canis lupus familiaris (dog) / References: UniProt: P60058 |
#88: Protein/peptide | Mass: 3265.008 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Canis lupus familiaris (dog) / References: UniProt: P60467 |
-Non-polymers , 2 types, 305 molecules
#89: Chemical | ChemComp-ZN / #90: Chemical | ChemComp-MG / |
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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
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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 FIELDBright-field microscopy |
Image recording | Electron dose: 28 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
-Processing
CTF correction | Type: NONE |
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Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 12749 / Symmetry type: POINT |
Atomic model building | Protocol: RIGID BODY FIT |