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Open data
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Basic information
Entry | Database: PDB / ID: 7z22 | ||||||
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Title | Connexin43 gap junction channel structure in nanodisc | ||||||
![]() | Gap junction alpha-1 protein | ||||||
![]() | MEMBRANE PROTEIN / gap junction channel / connexin / cell communication | ||||||
Function / homology | ![]() gap junction channel activity involved in cardiac conduction electrical coupling / negative regulation of gonadotropin secretion / positive regulation of striated muscle tissue development / milk ejection reflex / positive regulation of morphogenesis of an epithelium / positive regulation of mesodermal cell differentiation / atrial ventricular junction remodeling / cell communication by chemical coupling / cell communication by electrical coupling / neuroblast migration ...gap junction channel activity involved in cardiac conduction electrical coupling / negative regulation of gonadotropin secretion / positive regulation of striated muscle tissue development / milk ejection reflex / positive regulation of morphogenesis of an epithelium / positive regulation of mesodermal cell differentiation / atrial ventricular junction remodeling / cell communication by chemical coupling / cell communication by electrical coupling / neuroblast migration / columnar/cuboidal epithelial cell maturation / negative regulation of trophoblast cell migration / microtubule-based transport / gap junction hemi-channel activity / monoatomic ion transmembrane transporter activity / regulation of bone remodeling / SARS-CoV-2 targets PDZ proteins in cell-cell junction / gap junction channel activity involved in cell communication by electrical coupling / regulation of ventricular cardiac muscle cell membrane depolarization / contractile muscle fiber / Oligomerization of connexins into connexons / Transport of connexins along the secretory pathway / glutathione transmembrane transporter activity / Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / gap junction assembly / atrial cardiac muscle cell action potential / Regulation of gap junction activity / cardiac conduction system development / regulation of atrial cardiac muscle cell membrane depolarization / cellular response to pH / connexin complex / fascia adherens / gap junction / cell-cell contact zone / Formation of annular gap junctions / Golgi-associated vesicle membrane / cell communication by electrical coupling involved in cardiac conduction / Gap junction degradation / bone remodeling / skeletal muscle tissue regeneration / gap junction channel activity / Gap junction assembly / regulation of bone mineralization / export across plasma membrane / adult heart development / regulation of ventricular cardiac muscle cell membrane repolarization / tight junction / glutamate secretion / blood vessel morphogenesis / lens development in camera-type eye / intermediate filament / xenobiotic transport / Mechanical load activates signaling by PIEZO1 and integrins in osteocytes / embryonic digit morphogenesis / maintenance of blood-brain barrier / positive regulation of stem cell proliferation / beta-tubulin binding / RHOJ GTPase cycle / RHOQ GTPase cycle / heart looping / establishment of mitotic spindle orientation / efflux transmembrane transporter activity / intercalated disc / alpha-tubulin binding / lateral plasma membrane / T cell proliferation / positive regulation of vascular associated smooth muscle cell proliferation / tubulin binding / protein tyrosine kinase binding / negative regulation of cell growth / beta-catenin binding / bone development / cellular response to amyloid-beta / male gonad development / neuron migration / osteoblast differentiation / cell junction / intracellular protein localization / cell-cell signaling / positive regulation of cold-induced thermogenesis / heart development / scaffold protein binding / monoatomic ion transmembrane transport / spermatogenesis / in utero embryonic development / positive regulation of canonical NF-kappaB signal transduction / apical plasma membrane / membrane raft / Golgi membrane / signaling receptor binding / negative regulation of gene expression / focal adhesion / intracellular membrane-bounded organelle / positive regulation of gene expression / endoplasmic reticulum membrane / Golgi apparatus / signal transduction / mitochondrion / nucleoplasm / nucleus Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.95 Å | ||||||
![]() | Qi, C. / Korkhov, M.V. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of the connexin-43 gap junction channel in a putative closed state. Authors: Chao Qi / Silvia Acosta Gutierrez / Pia Lavriha / Alaa Othman / Diego Lopez-Pigozzi / Erva Bayraktar / Dina Schuster / Paola Picotti / Nicola Zamboni / Mario Bortolozzi / Francesco Luigi ...Authors: Chao Qi / Silvia Acosta Gutierrez / Pia Lavriha / Alaa Othman / Diego Lopez-Pigozzi / Erva Bayraktar / Dina Schuster / Paola Picotti / Nicola Zamboni / Mario Bortolozzi / Francesco Luigi Gervasio / Volodymyr M Korkhov / ![]() ![]() ![]() ![]() Abstract: Gap junction channels (GJCs) mediate intercellular communication by connecting two neighbouring cells and enabling direct exchange of ions and small molecules. Cell coupling via connexin-43 (Cx43) ...Gap junction channels (GJCs) mediate intercellular communication by connecting two neighbouring cells and enabling direct exchange of ions and small molecules. Cell coupling via connexin-43 (Cx43) GJCs is important in a wide range of cellular processes in health and disease (Churko and Laird, 2013; Liang et al., 2020; Poelzing and Rosenbaum, 2004), yet the structural basis of Cx43 function and regulation has not been determined until now. Here, we describe the structure of a human Cx43 GJC solved by cryo-EM and single particle analysis at 2.26 Å resolution. The pore region of Cx43 GJC features several lipid-like densities per Cx43 monomer, located close to a putative lateral access site at the monomer boundary. We found a previously undescribed conformation on the cytosolic side of the pore, formed by the N-terminal domain and the transmembrane helix 2 of Cx43 and stabilized by a small molecule. Structures of the Cx43 GJC and hemichannels (HCs) in nanodiscs reveal a similar gate arrangement. The features of the Cx43 GJC and HC cryo-EM maps and the channel properties revealed by molecular dynamics simulations suggest that the captured states of Cx43 are consistent with a closed state. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 421.6 KB | Display | ![]() |
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PDB format | ![]() | 340 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 14455MC ![]() 7z1tC ![]() 7z23C C: citing same article ( M: map data used to model this data |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 43061.336 Da / Num. of mol.: 12 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Has protein modification | Y | |
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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 |
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Sample preparation
Component | Name: Connexin43 gap junction channel / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 43 kDa/nm / Experimental value: YES |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
EM imaging optics | Energyfilter slit width: 20 eV |
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Processing
EM software | Name: EPU / Version: 2 / Category: image acquisition |
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CTF correction | Type: NONE |
3D reconstruction | Resolution: 2.95 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 10886 / Symmetry type: POINT |