+Open data
-Basic information
Entry | Database: PDB / ID: 8uip | ||||||
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Title | Cryo-EM Structure of Human Ninjurin1 curved oligomer | ||||||
Components | Ninjurin-1 | ||||||
Keywords | IMMUNE SYSTEM / Ninjurin1 / NINJ1 / inflammation / inflammasome / pyroptosis / plasma membrane rupture | ||||||
Function / homology | Function and homology information cell adhesion mediator activity / leukocyte chemotaxis involved in inflammatory response / membrane destabilizing activity / muscle cell differentiation / positive regulation of toll-like receptor 4 signaling pathway / tissue regeneration / programmed cell death / heterotypic cell-cell adhesion / pyroptotic inflammatory response / synaptic membrane ...cell adhesion mediator activity / leukocyte chemotaxis involved in inflammatory response / membrane destabilizing activity / muscle cell differentiation / positive regulation of toll-like receptor 4 signaling pathway / tissue regeneration / programmed cell death / heterotypic cell-cell adhesion / pyroptotic inflammatory response / synaptic membrane / lipopolysaccharide binding / protein homooligomerization / positive regulation of inflammatory response / positive regulation of angiogenesis / nervous system development / angiogenesis / killing of cells of another organism / cell adhesion / extracellular region / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.3 Å | ||||||
Authors | David, L. / Wu, H. | ||||||
Funding support | United States, 1items
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Citation | Journal: Cell / Year: 2024 Title: NINJ1 mediates plasma membrane rupture by cutting and releasing membrane disks. Authors: Liron David / Jazlyn P Borges / L Robert Hollingsworth / Allen Volchuk / Isabelle Jansen / Evelyn Garlick / Benjamin E Steinberg / Hao Wu / Abstract: The membrane protein NINJ1 mediates plasma membrane rupture in pyroptosis and other lytic cell death pathways. Here, we report the cryo-EM structure of a NINJ1 oligomer segmented from NINJ1 rings. ...The membrane protein NINJ1 mediates plasma membrane rupture in pyroptosis and other lytic cell death pathways. Here, we report the cryo-EM structure of a NINJ1 oligomer segmented from NINJ1 rings. Each NINJ1 subunit comprises amphipathic (⍺1, ⍺2) and transmembrane (TM) helices (⍺3, ⍺4) and forms a chain of subunits, mainly by the TM helices and ⍺1. ⍺3 and ⍺4 are kinked, and the Gly residues are important for function. The NINJ1 oligomer possesses a concave hydrophobic side that should face the membrane and a convex hydrophilic side formed by ⍺1 and ⍺2, presumably upon activation. This structural observation suggests that NINJ1 can form membrane disks, consistent with membrane fragmentation by recombinant NINJ1. Live-cell and super-resolution imaging uncover ring-like structures on the plasma membrane that are released into the culture supernatant. Released NINJ1 encircles a membrane inside, as shown by lipid staining. Therefore, NINJ1-mediated membrane disk formation is different from gasdermin-mediated pore formation, resulting in membrane loss and plasma membrane rupture. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8uip.cif.gz | 61.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8uip.ent.gz | 45.1 KB | Display | PDB format |
PDBx/mmJSON format | 8uip.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ui/8uip ftp://data.pdbj.org/pub/pdb/validation_reports/ui/8uip | HTTPS FTP |
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-Related structure data
Related structure data | 42301MC 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: 16356.998 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NINJ1 / Production host: Escherichia phage EcSzw_1 (virus) / References: UniProt: Q92982 |
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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 |
-Sample preparation
Component | Name: Ninjurin 1 ring oligomer / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia phage EcSzw_1 (virus) |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
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 FIELDBright-field microscopy / Nominal defocus max: 2200 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 51.3 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
EM software | Name: SerialEM / Category: image acquisition |
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CTF correction | Type: NONE |
3D reconstruction | Resolution: 4.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 626231 / Symmetry type: POINT |
Atomic model building | Protocol: BACKBONE TRACE |