[English] 日本語
Yorodumi- EMDB-31496: Structure of connexin43/Cx43/GJA1 gap junction intercellular chan... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31496 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of connexin43/Cx43/GJA1 gap junction intercellular channel in nanodiscs with soybean lipids at pH ~8.0 | |||||||||
Map data | Sharpened map of human Cx43/GJA1 connexin gap junction channel in nanodiscs | |||||||||
Sample |
| |||||||||
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 / monoatomic ion transmembrane transporter activity / microtubule-based transport / regulation of bone remodeling / regulation of ventricular cardiac muscle cell membrane depolarization / SARS-CoV-2 targets PDZ proteins in cell-cell junction / 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 / skeletal muscle tissue regeneration / cardiac conduction system development / 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 / regulation of ventricular cardiac muscle cell membrane repolarization / glutamate secretion / tight junction / blood vessel morphogenesis / lens development in camera-type eye / xenobiotic transport / intermediate filament / embryonic digit morphogenesis / maintenance of blood-brain barrier / efflux transmembrane transporter activity / heart looping / positive regulation of stem cell proliferation / RHOJ GTPase cycle / 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 / protein tyrosine kinase binding / tubulin binding / neuron migration / negative regulation of cell growth / beta-catenin binding / osteoblast differentiation / male gonad development / cellular response to amyloid-beta / positive regulation of cold-induced thermogenesis / protein localization / cell junction / cell-cell signaling / monoatomic ion transmembrane transport / heart development / scaffold protein binding / spermatogenesis / positive regulation of canonical NF-kappaB signal transduction / in utero embryonic development / apical plasma membrane / membrane raft / Golgi membrane / intracellular membrane-bounded organelle / negative regulation of gene expression / 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 | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
Authors | Lee HJ / Cha HJ / Jeong H / Lee SN / Lee CW / Woo JS | |||||||||
Funding support | Korea, Republic Of, 1 items
| |||||||||
Citation | Journal: Nat Commun / Year: 2023 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 |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_31496.map.gz | 482.7 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-31496-v30.xml emd-31496.xml | 10.1 KB 10.1 KB | Display Display | EMDB header |
Images | emd_31496.png | 40 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31496 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31496 | HTTPS FTP |
-Validation report
Summary document | emd_31496_validation.pdf.gz | 559.2 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_31496_full_validation.pdf.gz | 558.8 KB | Display | |
Data in XML | emd_31496_validation.xml.gz | 8.1 KB | Display | |
Data in CIF | emd_31496_validation.cif.gz | 9.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31496 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31496 | HTTPS FTP |
-Related structure data
Related structure data | 7f93MC 7f92C 7f94C 7xq9C 7xqbC 7xqdC 7xqfC 7xqgC 7xqhC 7xqiC 7xqjC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_31496.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Sharpened map of human Cx43/GJA1 connexin gap junction channel in nanodiscs | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.5235 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Sample components
-Entire : Dodecameric complex of human Cx43/GJA1 in lipid nanodiscs (Soybea...
Entire | Name: Dodecameric complex of human Cx43/GJA1 in lipid nanodiscs (Soybean polar extract) |
---|---|
Components |
|
-Supramolecule #1: Dodecameric complex of human Cx43/GJA1 in lipid nanodiscs (Soybea...
Supramolecule | Name: Dodecameric complex of human Cx43/GJA1 in lipid nanodiscs (Soybean polar extract) type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 Details: Human Cx43 gap junction channel with gate-covering NTH conformation |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
-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 |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 43.061336 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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 |
-Macromolecule #2: TETRADECANE
Macromolecule | Name: TETRADECANE / type: ligand / ID: 2 / Number of copies: 120 / Formula: C14 |
---|---|
Molecular weight | Theoretical: 198.388 Da |
Chemical component information | ChemComp-C14: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 28341 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |