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Open data
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Basic information
Entry | Database: PDB / ID: 8qfd | |||||||||||||||
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Title | UFL1 E3 ligase bound 60S ribosome | |||||||||||||||
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![]() | LIGASE / UFM1 / Ribosome / Complex | |||||||||||||||
Function / homology | ![]() UFM1 ligase activity / positive regulation of reticulophagy / UFM1 transferase activity / protein K69-linked ufmylation / positive regulation of proteolysis involved in protein catabolic process / protein ufmylation / negative regulation of IRE1-mediated unfolded protein response / regulation of proteasomal ubiquitin-dependent protein catabolic process / negative regulation of T cell mediated immune response to tumor cell / negative regulation of T cell activation ...UFM1 ligase activity / positive regulation of reticulophagy / UFM1 transferase activity / protein K69-linked ufmylation / positive regulation of proteolysis involved in protein catabolic process / protein ufmylation / negative regulation of IRE1-mediated unfolded protein response / regulation of proteasomal ubiquitin-dependent protein catabolic process / negative regulation of T cell mediated immune response to tumor cell / negative regulation of T cell activation / regulation of intracellular estrogen receptor signaling pathway / translation at presynapse / embryonic brain development / exit from mitosis / eukaryotic 80S initiation complex / negative regulation of protein neddylation / response to insecticide / regulation of G1 to G0 transition / axial mesoderm development / negative regulation of formation of translation preinitiation complex / regulation of translation involved in cellular response to UV / ribosomal protein import into nucleus / optic nerve development / protein-DNA complex disassembly / 90S preribosome assembly / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / retinal ganglion cell axon guidance / ribosome disassembly / Transferases; Acyltransferases; Aminoacyltransferases / regulation of canonical NF-kappaB signal transduction / GAIT complex / A band / positive regulation of DNA damage response, signal transduction by p53 class mediator / TORC2 complex binding / alpha-beta T cell differentiation / reticulophagy / G1 to G0 transition / middle ear morphogenesis / response to L-glutamate / cytoplasmic side of rough endoplasmic reticulum membrane / negative regulation of ubiquitin protein ligase activity / negative regulation of NF-kappaB transcription factor activity / homeostatic process / response to aldosterone / macrophage chemotaxis / lung morphogenesis / Protein hydroxylation / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / positive regulation of signal transduction by p53 class mediator / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of ubiquitin-dependent protein catabolic process / blastocyst development / cellular response to actinomycin D / Viral mRNA Translation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / hematopoietic stem cell differentiation / protein localization to nucleus / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / protein targeting / protein-RNA complex assembly / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / maturation of LSU-rRNA / rough endoplasmic reticulum / translation regulator activity / Maturation of protein E / Maturation of protein E / positive regulation of glial cell proliferation / ER Quality Control Compartment (ERQC) / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / negative regulation of protein ubiquitination / Alpha-protein kinase 1 signaling pathway / positive regulation of autophagy / cytosolic ribosome / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Endosomal Sorting Complex Required For Transport (ESCRT) / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Negative regulation of FLT3 / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / embryo implantation / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Constitutive Signaling by NOTCH1 HD Domain Mutants / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1,TRAF6-dependent induction of TAK1 complex / rescue of stalled ribosome / TICAM1-dependent activation of IRF3/IRF7 Similarity search - Function | |||||||||||||||
Biological species | ![]() | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.2 Å | |||||||||||||||
![]() | Makhlouf, L. / Kulathu, Y. / Zeqiraj, E. | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: The UFM1 E3 ligase recognizes and releases 60S ribosomes from ER translocons. Authors: Linda Makhlouf / Joshua J Peter / Helge M Magnussen / Rohan Thakur / David Millrine / Thomas C Minshull / Grace Harrison / Joby Varghese / Frederic Lamoliatte / Martina Foglizzo / Thomas ...Authors: Linda Makhlouf / Joshua J Peter / Helge M Magnussen / Rohan Thakur / David Millrine / Thomas C Minshull / Grace Harrison / Joby Varghese / Frederic Lamoliatte / Martina Foglizzo / Thomas Macartney / Antonio N Calabrese / Elton Zeqiraj / Yogesh Kulathu / ![]() Abstract: Stalled ribosomes at the endoplasmic reticulum (ER) are covalently modified with the ubiquitin-like protein UFM1 on the 60S ribosomal subunit protein RPL26 (also known as uL24). This modification, ...Stalled ribosomes at the endoplasmic reticulum (ER) are covalently modified with the ubiquitin-like protein UFM1 on the 60S ribosomal subunit protein RPL26 (also known as uL24). This modification, which is known as UFMylation, is orchestrated by the UFM1 ribosome E3 ligase (UREL) complex, comprising UFL1, UFBP1 and CDK5RAP3 (ref. ). However, the catalytic mechanism of UREL and the functional consequences of UFMylation are unclear. Here we present cryo-electron microscopy structures of UREL bound to 60S ribosomes, revealing the basis of its substrate specificity. UREL wraps around the 60S subunit to form a C-shaped clamp architecture that blocks the tRNA-binding sites at one end, and the peptide exit tunnel at the other. A UFL1 loop inserts into and remodels the peptidyl transferase centre. These features of UREL suggest a crucial function for UFMylation in the release and recycling of stalled or terminated ribosomes from the ER membrane. In the absence of functional UREL, 60S-SEC61 translocon complexes accumulate at the ER membrane, demonstrating that UFMylation is necessary for releasing SEC61 from 60S subunits. Notably, this release is facilitated by a functional switch of UREL from a 'writer' to a 'reader' module that recognizes its product-UFMylated 60S ribosomes. Collectively, we identify a fundamental role for UREL in dissociating 60S subunits from the SEC61 translocon and the basis for UFMylation in regulating protein homeostasis at the ER. | |||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 3.1 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.6 MB | Display | ![]() |
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Full document | ![]() | 1.6 MB | Display | |
Data in XML | ![]() | 193.4 KB | Display | |
Data in CIF | ![]() | 357.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 18382MC ![]() 8bzrC ![]() 8c0dC ![]() 8qfcC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-RNA chain , 3 types, 3 molecules 578
#1: RNA chain | Mass: 1640230.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#2: RNA chain | Mass: 38385.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#3: RNA chain | Mass: 50449.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
+60S ribosomal protein ... , 38 types, 38 molecules ABCDEGHIJLMNOPQRSTUVWXYZabcdef...
-Protein , 4 types, 4 molecules Fjms
#9: Protein | Mass: 29290.973 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#38: Protein | Mass: 11111.032 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#41: Protein | Mass: 14758.394 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#45: Protein | Mass: 91591.234 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: O94874, Transferases; Acyltransferases; Aminoacyltransferases |
-Non-polymers , 3 types, 2330 molecules 




#46: Chemical | ChemComp-MG / #47: Chemical | ChemComp-ZN / #48: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | N |
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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) | Organism: ![]() ![]() | ||||||||||||||||||
Buffer solution | pH: 7.5 Details: 25 mM HEPES pH 7.5, 50 mM KCl, 5 mM MgCl2, 2 mM DTT | ||||||||||||||||||
Specimen | Conc.: 7.7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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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 / Nominal magnification: 165000 X / Nominal defocus max: 2000 nm / Nominal defocus min: 200 nm |
Image recording | Average exposure time: 2.67 sec. / Electron dose: 33.4 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 59394 |
EM imaging optics | Energyfilter name: TFS Selectris X / Energyfilter slit width: 10 eV |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
3D reconstruction | Resolution: 2.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 299008 / Symmetry type: POINT |