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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 / transferase complex / regulation of intracellular estrogen receptor signaling pathway / negative regulation of T cell mediated immune response to tumor cell / regulation of proteasomal ubiquitin-dependent protein catabolic process ...UFM1 ligase activity / positive regulation of reticulophagy / UFM1 transferase activity / protein K69-linked ufmylation / protein ufmylation / negative regulation of IRE1-mediated unfolded protein response / transferase complex / regulation of intracellular estrogen receptor signaling pathway / negative regulation of T cell mediated immune response to tumor cell / regulation of proteasomal ubiquitin-dependent protein catabolic process / embryonic brain development / translation at presynapse / Transferases; Acyltransferases; Aminoacyltransferases / response to insecticide / eukaryotic 80S initiation complex / ribosome disassembly / ribosomal protein import into nucleus / regulation of G1 to G0 transition / regulation of canonical NF-kappaB signal transduction / G1 to G0 transition / reticulophagy / negative regulation of formation of translation preinitiation complex / GAIT complex / hematopoietic stem cell differentiation / TORC2 complex binding / negative regulation of T cell activation / A band / cytoplasmic side of rough endoplasmic reticulum membrane / regulation of translation involved in cellular response to UV / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / negative regulation of myoblast fusion / response to aldosterone / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator / Protein hydroxylation / SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST) / PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA / protein localization to nucleus / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / protein targeting / Eukaryotic Translation Termination / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / ubiquitin ligase inhibitor activity / Viral mRNA Translation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / positive regulation of signal transduction by p53 class mediator / GTP hydrolysis and joining of the 60S ribosomal subunit / embryo implantation / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / DNA damage checkpoint signaling / maturation of LSU-rRNA / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / negative regulation of ubiquitin-dependent protein catabolic process / translation regulator activity / rough endoplasmic reticulum / negative regulation of protein ubiquitination / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / Maturation of protein E / Maturation of protein E / positive regulation of autophagy / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / response to endoplasmic reticulum stress / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Prevention of phagosomal-lysosomal fusion / Endosomal Sorting Complex Required For Transport (ESCRT) / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Negative regulation of FLT3 / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / Constitutive Signaling by NOTCH1 HD Domain Mutants / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1,TRAF6-dependent induction of TAK1 complex / Activation of STAT3 by cadherin engagement / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / Downregulation of ERBB4 signaling / erythrocyte differentiation / APC-Cdc20 mediated degradation of Nek2A / Regulation of FZD by ubiquitination / p75NTR recruits signalling complexes / InlA-mediated entry of Listeria monocytogenes into host cells / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / regulation of signal transduction by p53 class mediator / NF-kB is activated and signals survival / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Regulation of pyruvate metabolism / Pexophagy / PD-L1(CD274) glycosylation and translocation to plasma membrane 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 (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: 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