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- EMDB-33391: Structure of connexin43/Cx43/GJA1 gap junction intercellular chan... -
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Open data
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Basic information
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Title | Structure of connexin43/Cx43/GJA1 gap junction intercellular channel in GDN detergents at pH ~8.0 | |||||||||
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![]() | Cx43 / Connexin / Gap junction channel / Gating mechanism / Membrane protein | |||||||||
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 / regulation of bone remodeling / monoatomic ion transmembrane transporter activity / SARS-CoV-2 targets PDZ proteins in cell-cell junction / gap junction channel activity involved in cell communication by electrical coupling / contractile muscle fiber / regulation of ventricular cardiac muscle cell membrane depolarization / 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 / cellular response to pH / cardiac conduction system development / regulation of atrial cardiac muscle cell membrane depolarization / connexin complex / fascia adherens / Golgi-associated vesicle membrane / Formation of annular gap junctions / gap junction / cell-cell contact zone / Gap junction degradation / cell communication by electrical coupling involved in cardiac conduction / skeletal muscle tissue regeneration / bone remodeling / 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 / embryonic digit morphogenesis / maintenance of blood-brain barrier / positive regulation of stem cell proliferation / beta-tubulin binding / RHOJ GTPase cycle / heart looping / RHOQ GTPase cycle / 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 / neuron migration / negative regulation of cell growth / bone development / beta-catenin binding / cellular response to amyloid-beta / male gonad development / osteoblast differentiation / cell junction / protein localization / cell-cell signaling / positive regulation of cold-induced thermogenesis / heart development / scaffold protein binding / monoatomic ion transmembrane transport / spermatogenesis / positive regulation of canonical NF-kappaB signal transduction / in utero embryonic development / apical plasma membrane / membrane raft / Golgi membrane / signaling receptor binding / negative regulation of gene expression / intracellular membrane-bounded organelle / focal adhesion / positive regulation of gene expression / endoplasmic reticulum membrane / Golgi apparatus / signal transduction / mitochondrion / nucleoplasm / nucleus / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
![]() | Lee HJ / Cha HJ / Jeong H / Lee SN / Lee CW / Woo JS | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Conformational changes in the human Cx43/GJA1 gap junction channel visualized using cryo-EM. Authors: Hyuk-Joon Lee / Hyung Jin Cha / Hyeongseop Jeong / Seu-Na Lee / Chang-Won Lee / Minsoo Kim / Jejoong Yoo / Jae-Sung Woo / ![]() Abstract: Connexin family proteins assemble into hexameric hemichannels in the cell membrane. The hemichannels dock together between two adjacent membranes to form gap junction intercellular channels (GJIChs). ...Connexin family proteins assemble into hexameric hemichannels in the cell membrane. The hemichannels dock together between two adjacent membranes to form gap junction intercellular channels (GJIChs). We report the cryo-electron microscopy structures of Cx43 GJICh, revealing the dynamic equilibrium state of various channel conformations in detergents and lipid nanodiscs. We identify three different N-terminal helix conformations of Cx43-gate-covering (GCN), pore-lining (PLN), and flexible intermediate (FIN)-that are randomly distributed in purified GJICh particles. The conformational equilibrium shifts to GCN by cholesteryl hemisuccinates and to PLN by C-terminal truncations and at varying pH. While GJIChs that mainly comprise GCN protomers are occluded by lipids, those containing conformationally heterogeneous protomers show markedly different pore sizes. We observe an α-to-π-helix transition in the first transmembrane helix, which creates a side opening to the membrane in the FIN and PLN conformations. This study provides basic structural information to understand the mechanisms of action and regulation of Cx43 GJICh. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.9 KB 13.9 KB | Display Display | ![]() |
Images | ![]() | 37.9 KB | ||
Filedesc metadata | ![]() | 5.2 KB | ||
Others | ![]() ![]() | 59.2 MB 59.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 993.6 KB | Display | ![]() |
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Full document | ![]() | 993.2 KB | Display | |
Data in XML | ![]() | 12.4 KB | Display | |
Data in CIF | ![]() | 14.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7xq9MC ![]() 7f92C ![]() 7f93C ![]() 7f94C ![]() 7xqbC ![]() 7xqdC ![]() 7xqfC ![]() 7xqgC ![]() 7xqhC ![]() 7xqiC ![]() 7xqjC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | sharpened map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.144 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: half map
File | emd_33391_half_map_1.map | ||||||||||||
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Annotation | half map | ||||||||||||
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Density Histograms |
-Half map: half map
File | emd_33391_half_map_2.map | ||||||||||||
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Annotation | half map | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Dodecameric complex of human Cx43/GJA1 in detergents (GDN)
Entire | Name: Dodecameric complex of human Cx43/GJA1 in detergents (GDN) |
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Components |
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-Supramolecule #1: Dodecameric complex of human Cx43/GJA1 in detergents (GDN)
Supramolecule | Name: Dodecameric complex of human Cx43/GJA1 in detergents (GDN) type: complex / ID: 1 / Parent: 0 / Macromolecule list: all Details: Human Cx43 gap junction channel with gate-covering NTH conformation |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Gap junction alpha-1 protein
Macromolecule | Name: Gap junction alpha-1 protein / type: protein_or_peptide / ID: 1 / Number of copies: 12 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 43.061336 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MGDWSALGKL LDKVQAYSTA GGKVWLSVLF IFRILLLGTA VESAWGDEQS AFRCNTQQPG CENVCYDKSF PISHVRFWVL QIIFVSVPT LLYLAHVFYV MRKEEKLNKK EEELKVAQTD GVNVDMHLKQ IEIKKFKYGI EEHGKVKMRG GLLRTYIISI L FKSIFEVA ...String: MGDWSALGKL LDKVQAYSTA GGKVWLSVLF IFRILLLGTA VESAWGDEQS AFRCNTQQPG CENVCYDKSF PISHVRFWVL QIIFVSVPT LLYLAHVFYV MRKEEKLNKK EEELKVAQTD GVNVDMHLKQ IEIKKFKYGI EEHGKVKMRG GLLRTYIISI L FKSIFEVA FLLIQWYIYG FSLSAVYTCK RDPCPHQVDC FLSRPTEKTI FIIFMLVVSL VSLALNIIEL FYVFFKGVKD RV KGKSDPY HATSGALSPA KDCGSQKYAY FNGCSSPTAP LSPMSPPGYK LVTGDRNNSS CRNYNKQASE QNWANYSAEQ NRM GQAGST ISNSHAQPFD FPDDNQNSKK LAAGHELQPL AIVDQRPSSR ASSRASSRPR PDDLEI UniProtKB: Gap junction alpha-1 protein |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 1.2 µm |
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Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 32618 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |