+Open data
-Basic information
Entry | Database: PDB / ID: 8c0d | ||||||
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Title | UFL1/DDRGK1 bound to UFC1 | ||||||
Components |
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Keywords | LIGASE / UFM1 / E3 ligase / ubiquitin / UFBP1 | ||||||
Function / homology | Function and homology information UFM1 conjugating enzyme activity / UFM1 ligase activity / UFM1 transferase activity / positive regulation of metallopeptidase activity / protein ufmylation / protein K69-linked ufmylation / positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding / positive regulation of protein localization to endoplasmic reticulum / negative regulation of IRE1-mediated unfolded protein response / regulation of proteasomal ubiquitin-dependent protein catabolic process ...UFM1 conjugating enzyme activity / UFM1 ligase activity / UFM1 transferase activity / positive regulation of metallopeptidase activity / protein ufmylation / protein K69-linked ufmylation / positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding / positive regulation of protein localization to endoplasmic reticulum / negative regulation of IRE1-mediated unfolded protein response / regulation of proteasomal ubiquitin-dependent protein catabolic process / positive regulation of I-kappaB phosphorylation / positive regulation of cell cycle G1/S phase transition / protein localization to endoplasmic reticulum / regulation of intracellular estrogen receptor signaling pathway / positive regulation of proteasomal protein catabolic process / Transferases; Acyltransferases; Aminoacyltransferases / cartilage development / regulation of canonical NF-kappaB signal transduction / reticulophagy / response to L-glutamate / negative regulation of NF-kappaB transcription factor activity / ubiquitin-like protein ligase binding / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / RHOA GTPase cycle / hematopoietic stem cell differentiation / positive regulation of autophagy / positive regulation of glial cell proliferation / negative regulation of protein ubiquitination / response to endoplasmic reticulum stress / erythrocyte differentiation / DNA damage checkpoint signaling / regulation of protein stability / brain development / osteoblast differentiation / regulation of protein localization / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / site of double-strand break / positive regulation of NF-kappaB transcription factor activity / regulation of inflammatory response / RNA polymerase II-specific DNA-binding transcription factor binding / mitochondrial outer membrane / positive regulation of cell migration / neuron projection / negative regulation of gene expression / DNA repair / DNA damage response / positive regulation of cell population proliferation / positive regulation of gene expression / endoplasmic reticulum membrane / nucleolus / negative regulation of apoptotic process / protein kinase binding / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / protein-containing complex / extracellular exosome / membrane / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.564 Å | ||||||
Authors | Magnussen, H.M. / Kulathu, Y. | ||||||
Funding support | United Kingdom, 1items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8c0d.cif.gz | 825.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8c0d.ent.gz | 527.8 KB | Display | PDB format |
PDBx/mmJSON format | 8c0d.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8c0d_validation.pdf.gz | 479.5 KB | Display | wwPDB validaton report |
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Full document | 8c0d_full_validation.pdf.gz | 491.1 KB | Display | |
Data in XML | 8c0d_validation.xml.gz | 30.6 KB | Display | |
Data in CIF | 8c0d_validation.cif.gz | 42.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c0/8c0d ftp://data.pdbj.org/pub/pdb/validation_reports/c0/8c0d | HTTPS FTP |
-Related structure data
Related structure data | 8bzrC 8qfcC 8qfdC C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
NCS ensembles :
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-Components
#1: Protein | Mass: 22350.311 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: UFL1, KIAA0776, MAXER, NLBP, RCAD / Production host: Escherichia coli (E. coli) References: UniProt: O94874, Transferases; Acyltransferases; Aminoacyltransferases #2: Protein | Mass: 12177.643 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DDRGK1, C20orf116, UFBP1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q96HY6 #3: Protein | Mass: 19569.482 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: UFC1, CGI-126, HSPC155 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9Y3C8 #4: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.99 Å3/Da / Density % sol: 58.91 % |
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Crystal grow | Temperature: 292 K / Method: vapor diffusion, hanging drop / pH: 7.2 / Details: 0.1M HEPES, 1.03M Li2SO4 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID23-2 / Wavelength: 0.873128 Å |
Detector | Type: DECTRIS PILATUS3 X 2M / Detector: PIXEL / Date: Jun 9, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.873128 Å / Relative weight: 1 |
Reflection | Resolution: 2.564→65.732 Å / Num. obs: 25858 / % possible obs: 93.8 % / Redundancy: 12.8 % / CC1/2: 0.997 / Net I/σ(I): 8.2 |
Reflection shell | Resolution: 2.564→2.892 Å / Num. unique obs: 1293 / CC1/2: 0.674 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.564→65.732 Å / Cor.coef. Fo:Fc: 0.914 / Cor.coef. Fo:Fc free: 0.86 / SU B: 30.585 / SU ML: 0.293 / Cross valid method: FREE R-VALUE / ESU R Free: 0.452 Details: Hydrogens have been added in their riding positions
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL PLUS MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 47.927 Å2
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Refinement step | Cycle: LAST / Resolution: 2.564→65.732 Å
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Refine LS restraints |
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Refine LS restraints NCS | Auth asym-ID: A / Refine-ID: X-RAY DIFFRACTION / Type: tight positional; tight thermal / Weight Biso : 0.5 / Weight position: 0.05
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group | Selection: ALL |