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- EMDB-33397: Hemichannel-focused structure of C-terminal truncated connexin43/... -
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Basic information
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Title | Hemichannel-focused structure of C-terminal truncated connexin43/Cx43/GJA1 gap junction intercellular channel in POPE nanodiscs (FIN conformation) | |||||||||
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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 / gap junction hemi-channel activity / negative regulation of trophoblast cell migration / microtubule-based transport / monoatomic ion transmembrane transporter activity / regulation of bone remodeling / 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 / glutathione transmembrane transporter activity / Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / gap junction assembly / cellular response to pH / atrial cardiac muscle cell action potential / Regulation of gap junction activity / skeletal muscle tissue regeneration / cardiac conduction system development / connexin complex / regulation of atrial cardiac muscle cell membrane depolarization / Golgi-associated vesicle membrane / Formation of annular gap junctions / fascia adherens / Gap junction degradation / cell communication by electrical coupling involved in cardiac conduction / cell-cell contact zone / gap junction / Gap junction assembly / gap junction channel activity / bone remodeling / export across plasma membrane / adult heart development / regulation of bone mineralization / xenobiotic transport / regulation of ventricular cardiac muscle cell membrane repolarization / glutamate secretion / tight junction / blood vessel morphogenesis / lens development in camera-type eye / intermediate filament / embryonic digit morphogenesis / maintenance of blood-brain barrier / positive regulation of stem cell proliferation / beta-tubulin binding / heart looping / RHOJ GTPase cycle / RHOQ GTPase cycle / efflux transmembrane transporter activity / establishment of mitotic spindle orientation / intercalated disc / lateral plasma membrane / alpha-tubulin binding / T cell proliferation / monoatomic ion transmembrane transport / positive regulation of vascular associated smooth muscle cell proliferation / tubulin binding / protein tyrosine kinase binding / neuron migration / bone development / negative regulation of cell growth / beta-catenin binding / osteoblast differentiation / cellular response to amyloid-beta / male gonad development / protein localization / cell junction / cell-cell signaling / heart development / positive regulation of cold-induced thermogenesis / scaffold protein binding / spermatogenesis / 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 | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 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 | ![]() | 48.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14 KB 14 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.1 KB | Display | ![]() |
Images | ![]() | 8.8 KB | ||
Others | ![]() ![]() | 48.6 MB 48.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7xqiMC ![]() 7f92C ![]() 7f93C ![]() 7f94C ![]() 7xq9C ![]() 7xqbC ![]() 7xqdC ![]() 7xqfC ![]() 7xqgC ![]() 7xqhC ![]() 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 | unsharpened map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.848 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_33397_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: half map
File | emd_33397_half_map_2.map | ||||||||||||
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Annotation | half map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Dodecameric complex of C-terminal deletion mutant of human Cx43/G...
Entire | Name: Dodecameric complex of C-terminal deletion mutant of human Cx43/GJA1 (Cx43-M257) in lipid nanodiscs (POPE) |
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Components |
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-Supramolecule #1: Dodecameric complex of C-terminal deletion mutant of human Cx43/G...
Supramolecule | Name: Dodecameric complex of C-terminal deletion mutant of human Cx43/GJA1 (Cx43-M257) in lipid nanodiscs (POPE) type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all Details: Hemichannel of Human Cx43-M257 gap junction channel with flexible-intermediate 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: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 29.396547 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 |
-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 | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 72.42 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.9 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |