+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-18382 | |||||||||||||||
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Title | UFL1 E3 ligase bound 60S ribosome | |||||||||||||||
Map data | Sharpened map. | |||||||||||||||
Sample |
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Keywords | UFM1 / Ligase / Ribosome / Complex | |||||||||||||||
Function / homology | Function and homology information UFM1 ligase activity / UFM1 transferase activity / protein ufmylation / protein K69-linked ufmylation / negative regulation of IRE1-mediated unfolded protein response / regulation of proteasomal ubiquitin-dependent protein catabolic process / embryonic brain development / regulation of intracellular estrogen receptor signaling pathway / eukaryotic 80S initiation complex / negative regulation of protein neddylation ...UFM1 ligase activity / UFM1 transferase activity / protein ufmylation / protein K69-linked ufmylation / negative regulation of IRE1-mediated unfolded protein response / regulation of proteasomal ubiquitin-dependent protein catabolic process / embryonic brain development / regulation of intracellular estrogen receptor signaling pathway / eukaryotic 80S initiation complex / negative regulation of protein neddylation / translation at presynapse / axial mesoderm development / negative regulation of formation of translation preinitiation complex / ribosomal protein import into nucleus / 90S preribosome assembly / TORC2 complex binding / Transferases; Acyltransferases; Aminoacyltransferases / GAIT complex / middle ear morphogenesis / regulation of canonical NF-kappaB signal transduction / reticulophagy / cytoplasmic side of rough endoplasmic reticulum membrane / A band / alpha-beta T cell differentiation / regulation of G1 to G0 transition / exit from mitosis / 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 / response to L-glutamate / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / negative regulation of ubiquitin protein ligase activity / optic nerve development / response to aldosterone / retinal ganglion cell axon guidance / G1 to G0 transition / homeostatic process / negative regulation of NF-kappaB transcription factor activity / lung morphogenesis / Protein hydroxylation / macrophage chemotaxis / Peptide chain elongation / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / blastocyst development / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / protein localization to nucleus / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / hematopoietic stem cell differentiation / Major pathway of rRNA processing in the nucleolus and cytosol / protein-RNA complex assembly / protein targeting / cellular response to interleukin-4 / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / translation regulator activity / positive regulation of autophagy / cellular response to actinomycin D / cytosolic ribosome / rough endoplasmic reticulum / Maturation of protein E / positive regulation of glial cell proliferation / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / negative regulation of protein ubiquitination / Prevention of phagosomal-lysosomal fusion / 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 / Membrane binding and targetting of GAG proteins / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / Pexophagy / Regulation of innate immune responses to cytosolic DNA Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.2 Å | |||||||||||||||
Authors | Makhlouf L / Kulathu Y / Zeqiraj E | |||||||||||||||
Funding support | United Kingdom, European Union, 4 items
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Citation | Journal: Nature / Year: 2024 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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_18382.map.gz | 538.8 MB | EMDB map data format | |
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Header (meta data) | emd-18382-v30.xml emd-18382.xml | 70.8 KB 70.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_18382_fsc.xml | 19.4 KB | Display | FSC data file |
Images | emd_18382.png | 67.8 KB | ||
Masks | emd_18382_msk_1.map | 775.5 MB | Mask map | |
Filedesc metadata | emd-18382.cif.gz | 15.1 KB | ||
Others | emd_18382_additional_1.map.gz emd_18382_additional_2.map.gz emd_18382_half_map_1.map.gz emd_18382_half_map_2.map.gz | 389.6 MB 717.1 MB 720.8 MB 720.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-18382 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-18382 | HTTPS FTP |
-Validation report
Summary document | emd_18382_validation.pdf.gz | 1010.5 KB | Display | EMDB validaton report |
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Full document | emd_18382_full_validation.pdf.gz | 1010 KB | Display | |
Data in XML | emd_18382_validation.xml.gz | 29.5 KB | Display | |
Data in CIF | emd_18382_validation.cif.gz | 38.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18382 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18382 | HTTPS FTP |
-Related structure data
Related structure data | 8qfdMC 8bzrC 8c0dC 8qfcC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_18382.map.gz / Format: CCP4 / Size: 775.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Sharpened map. | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.74 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_18382_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: Raw map.
File | emd_18382_additional_1.map | ||||||||||||
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Annotation | Raw map. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: DeepEMhancer map.
File | emd_18382_additional_2.map | ||||||||||||
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Annotation | DeepEMhancer map. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_18382_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_18382_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : 60S ribosome bound by the UFM1 ribosome E3 ligase complex.
+Supramolecule #1: 60S ribosome bound by the UFM1 ribosome E3 ligase complex.
+Supramolecule #2: UFM1 ribosome E3 ligase complex
+Macromolecule #1: 28S rRNA
+Macromolecule #2: 5S rRNA
+Macromolecule #3: 5.8S rRNA
+Macromolecule #4: 60S ribosomal protein L8
+Macromolecule #5: 60S ribosomal protein L3
+Macromolecule #6: 60S ribosomal protein L4
+Macromolecule #7: 60S ribosomal protein L5
+Macromolecule #8: 60S ribosomal protein L6
+Macromolecule #9: Large ribosomal subunit protein uL30
+Macromolecule #10: 60S ribosomal protein L7a
+Macromolecule #11: 60S ribosomal protein L9
+Macromolecule #12: 60S ribosomal protein L10
+Macromolecule #13: 60S ribosomal protein L11
+Macromolecule #14: 60S ribosomal protein L13
+Macromolecule #15: 60S ribosomal protein L14
+Macromolecule #16: 60S ribosomal protein L15
+Macromolecule #17: 60S ribosomal protein L13a
+Macromolecule #18: 60S ribosomal protein L17
+Macromolecule #19: 60S ribosomal protein L18
+Macromolecule #20: 60S ribosomal protein L19
+Macromolecule #21: 60S ribosomal protein L18a
+Macromolecule #22: 60S ribosomal protein L21
+Macromolecule #23: 60S ribosomal protein L22
+Macromolecule #24: 60S ribosomal protein L23
+Macromolecule #25: 60S ribosomal protein L24
+Macromolecule #26: 60S ribosomal protein L23a
+Macromolecule #27: 60S ribosomal protein L26
+Macromolecule #28: 60S ribosomal protein L27
+Macromolecule #29: 60S ribosomal protein L27a
+Macromolecule #30: 60S ribosomal protein L29
+Macromolecule #31: 60S ribosomal protein L30
+Macromolecule #32: 60S ribosomal protein L31
+Macromolecule #33: 60S ribosomal protein L32
+Macromolecule #34: 60S ribosomal protein L35a
+Macromolecule #35: 60S ribosomal protein L34
+Macromolecule #36: 60S ribosomal protein L35
+Macromolecule #37: 60S ribosomal protein L36
+Macromolecule #38: Ribosomal protein L37
+Macromolecule #39: 60S ribosomal protein L38
+Macromolecule #40: 60S ribosomal protein L39
+Macromolecule #41: Ubiquitin-60S ribosomal protein L40
+Macromolecule #42: 60S ribosomal protein L36a
+Macromolecule #43: 60S ribosomal protein L37a
+Macromolecule #44: 60S ribosomal protein L28
+Macromolecule #45: E3 UFM1-protein ligase 1
+Macromolecule #46: MAGNESIUM ION
+Macromolecule #47: ZINC ION
+Macromolecule #48: water
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 7.7 mg/mL |
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Buffer | pH: 7.5 Details: 25 mM HEPES pH 7.5, 50 mM KCl, 5 mM MgCl2, 2 mM DTT |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: TFS Selectris X / Energy filter - Slit width: 10 eV |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 59394 / Average exposure time: 2.67 sec. / Average electron dose: 33.4 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.2 µm / Nominal magnification: 165000 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |