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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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Keywords | LIGASE / UFM1 / Ribosome / Complex | |||||||||||||||
| Function / homology | Function and homology informationUFM1 ligase activity / positive regulation of reticulophagy / UFM1 transferase activity / protein K69-linked ufmylation / 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 / 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 / embryonic brain development / translation at presynapse / exit from mitosis / optic nerve development / response to insecticide / eukaryotic 80S initiation complex / regulation of translation involved in cellular response to UV / negative regulation of protein neddylation / Transferases; Acyltransferases; Aminoacyltransferases / negative regulation of formation of translation preinitiation complex / axial mesoderm development / regulation of G1 to G0 transition / retinal ganglion cell axon guidance / ribosomal protein import into nucleus / regulation of canonical NF-kappaB signal transduction / response to L-glutamate / ribosome disassembly / protein-DNA complex disassembly / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / 90S preribosome assembly / reticulophagy / alpha-beta T cell differentiation / GAIT complex / positive regulation of DNA damage response, signal transduction by p53 class mediator / TORC2 complex binding / G1 to G0 transition / middle ear morphogenesis / : / cytoplasmic side of rough endoplasmic reticulum membrane / negative regulation of ubiquitin protein ligase activity / homeostatic process / macrophage chemotaxis / lung morphogenesis / cellular response to actinomycin D / positive regulation of natural killer cell proliferation / Protein hydroxylation / Peptide chain elongation / positive regulation of glial cell proliferation / positive regulation of protein binding / Selenocysteine synthesis / Formation of a pool of free 40S subunits / Eukaryotic Translation Termination / blastocyst development / hematopoietic stem cell differentiation / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / negative regulation of ubiquitin-dependent protein catabolic process / ubiquitin ligase inhibitor activity / Viral mRNA Translation / positive regulation of signal transduction by p53 class mediator / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / protein localization to nucleus / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / protein targeting / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / protein-RNA complex assembly / : / maturation of LSU-rRNA / rough endoplasmic reticulum / translation regulator activity / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / positive regulation of autophagy / Constitutive Signaling by NOTCH1 HD Domain Mutants / IRAK2 mediated activation of TAK1 complex / Prevention of phagosomal-lysosomal fusion / Alpha-protein kinase 1 signaling pathway / negative regulation of protein ubiquitination / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / Endosomal Sorting Complex Required For Transport (ESCRT) / Membrane binding and targetting of GAG proteins / Negative regulation of FLT3 / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / embryo implantation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / 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 / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B Similarity search - Function | |||||||||||||||
| Biological species | Homo sapiens (human) | |||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.2 Å | |||||||||||||||
Authors | Makhlouf, L. / Kulathu, Y. / Zeqiraj, E. | |||||||||||||||
| Funding support | United Kingdom, European Union, 4items
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Citation | Journal: Nature / Year: 2024Title: 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. | |||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 8qfd.cif.gz | 3.1 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8qfd.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 8qfd.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qf/8qfd ftp://data.pdbj.org/pub/pdb/validation_reports/qf/8qfd | HTTPS FTP |
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-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 F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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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) Homo sapiens (human) / Cell line: HEK293 / References: GenBank: 86475748 |
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| #2: RNA chain | Mass: 38385.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: HEK293 / References: GenBank: XR_007069046.1 |
| #3: RNA chain | Mass: 50449.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: HEK293 / References: GenBank: 555853 |
+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) Homo sapiens (human) / Cell line: HEK293 / References: UniProt: P18124 |
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| #38: Protein | Mass: 11111.032 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: HEK293 / References: UniProt: A0A5J5MXE5 |
| #41: Protein | Mass: 14758.394 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: HEK293 / References: UniProt: P62987 |
| #45: Protein | Mass: 91591.234 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: UFL1, KIAA0776, MAXER, NLBP, RCAD / Production host: ![]() 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 (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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| 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
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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 |
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About Yorodumi




Homo sapiens (human)
United Kingdom, European Union, 4items
Citation




PDBj


















































FIELD EMISSION GUN