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- PDB-6r7q: Structure of XBP1u-paused ribosome nascent chain complex with Sec61. -
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Open data
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Basic information
Entry | Database: PDB / ID: 6r7q | ||||||
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Title | Structure of XBP1u-paused ribosome nascent chain complex with Sec61. | ||||||
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![]() | RIBOSOME / translational pausing / XBP1 / UPR | ||||||
Function / homology | ![]() ATF6-mediated unfolded protein response / organelle organization / positive regulation of protein acetylation / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / response to insulin-like growth factor stimulus / membrane docking / positive regulation of vascular wound healing / positive regulation of lactation / sterol homeostasis / 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 / response to insulin-like growth factor stimulus / membrane docking / positive regulation of vascular wound healing / positive regulation of lactation / sterol homeostasis / IRE1alpha activates chaperones / positive regulation of plasma cell differentiation / ATF6 (ATF6-alpha) activates chaperone genes / endoplasmic reticulum Sec complex / pronephric nephron development / positive regulation of ERAD pathway / 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 / cellular response to fructose stimulus / protein-transporting ATPase activity / protein insertion into ER membrane / XBP1(S) activates chaperone genes / cellular response to laminar fluid shear stress / cellular response to nutrient / negative regulation of endoplasmic reticulum unfolded protein response / positive regulation of endothelial cell apoptotic process / SRP-dependent cotranslational protein targeting to membrane, translocation / cellular response to fluid shear stress / signal sequence binding / post-translational protein targeting to membrane, translocation / 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 / protein transmembrane transporter 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 / 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) / guanyl-nucleotide exchange factor activity / liver development Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 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
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 4.8 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | 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 ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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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) ![]() ![]() |
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#2: Protein | Mass: 21629.309 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#3: Protein | Mass: 24003.012 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#10: Protein | Mass: 9348.990 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#28: Protein | Mass: 13048.244 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#76: Protein | Mass: 24759.145 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#79: Protein | Mass: 29523.674 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#81: Protein | Mass: 27471.535 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-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) ![]() ![]() |
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#5: Protein | Mass: 17586.766 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#6: Protein | Mass: 7007.069 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#20: Protein | Mass: 34669.113 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#25: Protein | Mass: 8526.119 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#27: Protein | Mass: 17057.113 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#37: Protein | Mass: 24511.861 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#38: Protein | Mass: 19399.498 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#41: Protein | Mass: 16217.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#42: Protein | Mass: 24076.088 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#51: Protein | Mass: 14131.536 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#53: Protein | Mass: 15891.787 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#65: Protein | Mass: 10090.891 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#71: Protein | Mass: 10168.153 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#78: Protein | Mass: 25215.586 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#80: Protein | Mass: 21525.941 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#82: Protein | Mass: 14734.357 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#83: Protein | Mass: 16032.804 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#84: Protein | Mass: 15626.392 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
+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.) ![]() ![]() ![]() |
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#67: Protein/peptide | Mass: 6324.579 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-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) ![]() ![]() |
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#17: RNA chain | Mass: 24148.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#18: RNA chain | Mass: 1877.157 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
#19: RNA chain | Mass: 1148460.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#21: RNA chain | Mass: 38691.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#22: RNA chain | Mass: 48545.672 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#39: RNA chain | Mass: 548040.188 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-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) ![]() ![]() |
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#33: Protein | Mass: 28818.293 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#40: Protein | Mass: 24200.525 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#54: Protein | Mass: 15704.635 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#64: Protein | Mass: 11888.371 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#69: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-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) ![]() ![]() |
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#87: Protein | Mass: 7019.456 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#88: Protein/peptide | Mass: 3265.008 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Non-polymers , 2 types, 305 molecules ![](data/chem/img/ZN.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/MG.gif)
#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 |
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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
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 |