+Open data
-Basic information
Entry | Database: PDB / ID: 7z23 | ||||||
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Title | Connexin43 hemi channel in nanodisc | ||||||
Components | Gap junction alpha-1 protein | ||||||
Keywords | MEMBRANE PROTEIN / gap junction channel / connexin / cell communication | ||||||
Function / homology | Function and homology information 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 / columnar/cuboidal epithelial cell maturation ...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 / columnar/cuboidal epithelial cell maturation / glutathione transmembrane transporter activity / neuroblast migration / gap junction hemi-channel activity / negative regulation of trophoblast cell migration / microtubule-based transport / regulation of bone remodeling / monoatomic ion transmembrane transporter activity / SARS-CoV-2 targets PDZ proteins in cell-cell junction / regulation of ventricular cardiac muscle cell membrane depolarization / gap junction channel activity involved in cell communication by electrical coupling / contractile muscle fiber / Oligomerization of connexins into connexons / Transport of connexins along the secretory pathway / Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / gap junction assembly / atrial cardiac muscle cell action potential / cellular response to pH / Regulation of gap junction activity / cardiac conduction system development / skeletal muscle tissue regeneration / regulation of atrial cardiac muscle cell membrane depolarization / connexin complex / Golgi-associated vesicle membrane / Formation of annular gap junctions / fascia adherens / Gap junction degradation / export across plasma membrane / cell communication by electrical coupling involved in cardiac conduction / cell-cell contact zone / gap junction / bone remodeling / Gap junction assembly / gap junction channel activity / adult heart development / regulation of bone mineralization / glutamate secretion / regulation of ventricular cardiac muscle cell membrane repolarization / tight junction / blood vessel morphogenesis / lens development in camera-type eye / xenobiotic transport / intermediate filament / embryonic digit morphogenesis / maintenance of blood-brain barrier / positive regulation of stem cell proliferation / RHOJ GTPase cycle / heart looping / efflux transmembrane transporter activity / beta-tubulin binding / RHOQ GTPase cycle / establishment of mitotic spindle orientation / intercalated disc / lateral plasma membrane / alpha-tubulin binding / T cell proliferation / positive regulation of vascular associated smooth muscle cell proliferation / bone development / tubulin binding / protein tyrosine kinase binding / neuron migration / negative regulation of cell growth / beta-catenin binding / osteoblast differentiation / male gonad development / monoatomic ion transmembrane transport / cellular response to amyloid-beta / protein localization / positive regulation of cold-induced thermogenesis / cell junction / cell-cell signaling / heart development / spermatogenesis / scaffold protein binding / positive regulation of canonical NF-kappaB signal transduction / in utero embryonic development / apical plasma membrane / membrane raft / Golgi membrane / negative regulation of gene expression / intracellular membrane-bounded organelle / signaling receptor binding / focal adhesion / endoplasmic reticulum membrane / positive regulation of gene expression / Golgi apparatus / signal transduction / mitochondrion / nucleoplasm / nucleus / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.98 Å | ||||||
Authors | Qi, C. / Korkhov, M.V. | ||||||
Funding support | Switzerland, 1items
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Citation | Journal: Elife / Year: 2023 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7z23.cif.gz | 219.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7z23.ent.gz | 172.5 KB | Display | PDB format |
PDBx/mmJSON format | 7z23.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7z23_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 7z23_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7z23_validation.xml.gz | 46.6 KB | Display | |
Data in CIF | 7z23_validation.cif.gz | 62.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/z2/7z23 ftp://data.pdbj.org/pub/pdb/validation_reports/z2/7z23 | HTTPS FTP |
-Related structure data
Related structure data | 14456MC 7z1tC 7z22C C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 43061.336 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GJA1, GJAL / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P17302 |
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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: 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: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: HEK293 |
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 |
-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: 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 |
-Processing
EM software | Name: EPU / Version: 2 / Category: image acquisition |
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CTF correction | Type: NONE |
3D reconstruction | Resolution: 3.98 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 20526 / Symmetry type: POINT |