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Yorodumi- PDB-8ct1: CryoEM structure of human S-OPA1 assembled on lipid membrane in m... -
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-Basic information
Entry | Database: PDB / ID: 8ct1 | ||||||
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Title | CryoEM structure of human S-OPA1 assembled on lipid membrane in membrane-adjacent state | ||||||
Components | Dynamin-like 120 kDa protein, mitochondrial | ||||||
Keywords | MEMBRANE PROTEIN / GTPase / polymer / filament / membrane / remodeling / fusion / mitochondria | ||||||
Function / homology | Function and homology information Regulation of Apoptosis / mitochondrial inner membrane fusion / membrane tubulation / GTPase-dependent fusogenic activity / membrane bending activity / inner mitochondrial membrane organization / dynamin GTPase / cristae formation / phosphatidic acid binding / mitochondrial genome maintenance ...Regulation of Apoptosis / mitochondrial inner membrane fusion / membrane tubulation / GTPase-dependent fusogenic activity / membrane bending activity / inner mitochondrial membrane organization / dynamin GTPase / cristae formation / phosphatidic acid binding / mitochondrial genome maintenance / cardiolipin binding / mitochondrial fission / GTP metabolic process / mitochondrial fusion / axonal transport of mitochondrion / negative regulation of release of cytochrome c from mitochondria / positive regulation of interleukin-17 production / mitochondrial crista / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / positive regulation of T-helper 17 cell lineage commitment / axon cytoplasm / Mitochondrial protein degradation / visual perception / mitochondrion organization / neural tube closure / mitochondrial membrane / protein complex oligomerization / mitochondrial intermembrane space / cellular senescence / microtubule binding / mitochondrial outer membrane / microtubule / mitochondrial inner membrane / GTPase activity / dendrite / GTP binding / negative regulation of apoptotic process / apoptotic process / magnesium ion binding / mitochondrion / nucleoplasm / membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 4.8 Å | ||||||
Authors | Du Pont, K.E. / Aydin, H. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nature / Year: 2023 Title: Structural mechanism of mitochondrial membrane remodelling by human OPA1. Authors: Alexander von der Malsburg / Gracie M Sapp / Kelly E Zuccaro / Alexander von Appen / Frank R Moss / Raghav Kalia / Jeremy A Bennett / Luciano A Abriata / Matteo Dal Peraro / Martin van der ...Authors: Alexander von der Malsburg / Gracie M Sapp / Kelly E Zuccaro / Alexander von Appen / Frank R Moss / Raghav Kalia / Jeremy A Bennett / Luciano A Abriata / Matteo Dal Peraro / Martin van der Laan / Adam Frost / Halil Aydin / Abstract: Distinct morphologies of the mitochondrial network support divergent metabolic and regulatory processes that determine cell function and fate. The mechanochemical GTPase optic atrophy 1 (OPA1) ...Distinct morphologies of the mitochondrial network support divergent metabolic and regulatory processes that determine cell function and fate. The mechanochemical GTPase optic atrophy 1 (OPA1) influences the architecture of cristae and catalyses the fusion of the mitochondrial inner membrane. Despite its fundamental importance, the molecular mechanisms by which OPA1 modulates mitochondrial morphology are unclear. Here, using a combination of cellular and structural analyses, we illuminate the molecular mechanisms that are key to OPA1-dependent membrane remodelling and fusion. Human OPA1 embeds itself into cardiolipin-containing membranes through a lipid-binding paddle domain. A conserved loop within the paddle domain inserts deeply into the bilayer, further stabilizing the interactions with cardiolipin-enriched membranes. OPA1 dimerization through the paddle domain promotes the helical assembly of a flexible OPA1 lattice on the membrane, which drives mitochondrial fusion in cells. Moreover, the membrane-bending OPA1 oligomer undergoes conformational changes that pull the membrane-inserting loop out of the outer leaflet and contribute to the mechanics of membrane remodelling. Our findings provide a structural framework for understanding how human OPA1 shapes mitochondrial morphology and show us how human disease mutations compromise OPA1 functions. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ct1.cif.gz | 4.2 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8ct1.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8ct1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ct1_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 8ct1_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 8ct1_validation.xml.gz | 478.7 KB | Display | |
Data in CIF | 8ct1_validation.cif.gz | 758 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ct/8ct1 ftp://data.pdbj.org/pub/pdb/validation_reports/ct/8ct1 | HTTPS FTP |
-Related structure data
Related structure data | 26977MC 8ct9C M: map data used to model this data 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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-Components
#1: Protein | Mass: 111804.789 Da / Num. of mol.: 34 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: OPA1, KIAA0567 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: O60313, dynamin GTPase |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: OPA1 / Type: COMPLEX Details: Uniprot ID: O60313 - HUMAN OPA1, Dynamin-like 120 kDa protein, mitochondrial Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 0.82 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli BL21(DE3) (bacteria) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Cryogen name: ETHANE |
-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 defocus max: 1200 nm / Nominal defocus min: 500 nm |
Image recording | Average exposure time: 2 sec. / Electron dose: 82 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
-Processing
Software |
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: 128.634 ° / Axial rise/subunit: 7.73 Å / Axial symmetry: C1 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 139018 / Symmetry type: HELICAL | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 451.28 Å2 | ||||||||||||||||||||||||
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