+Open data
-Basic information
Entry | Database: PDB / ID: 8bzr | ||||||
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Title | UFC1-UFM1 conjugate | ||||||
Components |
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Keywords | LIGASE / ubiquitin-fold modifier conjugating enzyme 1 | ||||||
Function / homology | Function and homology information UFM1 conjugating enzyme activity / UFM1 transferase activity / protein ufmylation / protein K69-linked ufmylation / regulation of intracellular estrogen receptor signaling pathway / reticulophagy / negative regulation of protein import into nucleus / response to endoplasmic reticulum stress / brain development / negative regulation of apoptotic process ...UFM1 conjugating enzyme activity / UFM1 transferase activity / protein ufmylation / protein K69-linked ufmylation / regulation of intracellular estrogen receptor signaling pathway / reticulophagy / negative regulation of protein import into nucleus / response to endoplasmic reticulum stress / brain development / negative regulation of apoptotic process / endoplasmic reticulum / extracellular exosome / nucleus / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.781 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 | 8bzr.cif.gz | 259 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8bzr.ent.gz | 159.1 KB | Display | PDB format |
PDBx/mmJSON format | 8bzr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8bzr_validation.pdf.gz | 442.2 KB | Display | wwPDB validaton report |
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Full document | 8bzr_full_validation.pdf.gz | 442.2 KB | Display | |
Data in XML | 8bzr_validation.xml.gz | 12.3 KB | Display | |
Data in CIF | 8bzr_validation.cif.gz | 16.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bz/8bzr ftp://data.pdbj.org/pub/pdb/validation_reports/bz/8bzr | HTTPS FTP |
-Related structure data
Related structure data | 8c0dC 8qfcC 8qfdC 3evxS S: Starting model for refinement 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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1 |
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Unit cell |
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Components on special symmetry positions |
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-Components
#1: Protein | Mass: 19923.889 Da / Num. of mol.: 1 / Mutation: C116K 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 | ||||
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#2: Protein | Mass: 8995.383 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: UFM1, C13orf20, BM-002 / Production host: Escherichia coli (E. coli) / References: UniProt: P61960 | ||||
#3: Chemical | ChemComp-EDO / #4: Water | ChemComp-HOH / | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.48 Å3/Da / Density % sol: 50.45 % |
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Crystal grow | Temperature: 292 K / Method: vapor diffusion, sitting drop / pH: 8.5 / Details: 30% v/v PEG400, 0.1M Tris, 0.2M Na citrate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795 Å |
Detector | Type: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Apr 8, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 1.78→47.33 Å / Num. obs: 26839 / % possible obs: 99.1 % / Redundancy: 12.5 % / CC1/2: 0.998 / Net I/σ(I): 9.2 |
Reflection shell | Resolution: 1.78→1.81 Å / Redundancy: 7.5 % / Mean I/σ(I) obs: 0.5 / Num. unique obs: 1192 / CC1/2: 0.27 / % possible all: 88.6 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3evx Resolution: 1.781→47.334 Å / Cor.coef. Fo:Fc: 0.964 / Cor.coef. Fo:Fc free: 0.947 / SU B: 7.563 / SU ML: 0.102 / Cross valid method: FREE R-VALUE / ESU R: 0.114 / ESU R Free: 0.117 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: 32.094 Å2
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Refinement step | Cycle: LAST / Resolution: 1.781→47.334 Å
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Refine LS restraints |
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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 |