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Yorodumi- EMDB-33397: Hemichannel-focused structure of C-terminal truncated connexin43/... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33397 | |||||||||
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Title | Hemichannel-focused structure of C-terminal truncated connexin43/Cx43/GJA1 gap junction intercellular channel in POPE nanodiscs (FIN conformation) | |||||||||
Map data | unsharpened map | |||||||||
Sample |
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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 / columnar/cuboidal epithelial cell maturation / cell communication by electrical coupling ...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 / columnar/cuboidal epithelial cell maturation / cell communication by electrical coupling / neuroblast migration / gap junction hemi-channel activity / gap junction channel activity involved in cell communication by electrical coupling / negative regulation of trophoblast cell migration / regulation of bone remodeling / microtubule-based transport / monoatomic ion transmembrane transporter activity / SARS-CoV-2 targets PDZ proteins in cell-cell junction / glutathione transmembrane transporter activity / regulation of ventricular cardiac muscle cell membrane depolarization / Oligomerization of connexins into connexons / Transport of connexins along the secretory pathway / contractile muscle fiber / gap junction assembly / Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / cellular response to pH / atrial cardiac muscle cell action potential / Regulation of gap junction activity / connexin complex / skeletal muscle tissue regeneration / cardiac conduction system development / regulation of atrial cardiac muscle cell membrane depolarization / Formation of annular gap junctions / Golgi-associated vesicle membrane / Gap junction degradation / fascia adherens / Gap junction assembly / bone remodeling / gap junction channel activity / gap junction / cell-cell contact zone / export across plasma membrane / adult heart development / regulation of bone mineralization / glutamate secretion / regulation of ventricular cardiac muscle cell membrane repolarization / xenobiotic transport / tight junction / blood vessel morphogenesis / lens development in camera-type eye / intermediate filament / cell communication by electrical coupling involved in cardiac conduction / embryonic digit morphogenesis / maintenance of blood-brain barrier / beta-tubulin binding / positive regulation of stem cell proliferation / heart looping / RHOJ GTPase cycle / RHOQ GTPase cycle / efflux transmembrane transporter activity / establishment of mitotic spindle orientation / alpha-tubulin binding / intercalated disc / lateral plasma membrane / T cell proliferation / positive regulation of vascular associated smooth muscle cell proliferation / protein tyrosine kinase binding / tubulin binding / monoatomic ion transmembrane transport / neuron migration / bone development / protein localization / negative regulation of cell growth / beta-catenin binding / osteoblast differentiation / cellular response to amyloid-beta / male gonad development / cell-cell signaling / cell junction / positive regulation of cold-induced thermogenesis / heart development / scaffold protein binding / spermatogenesis / positive regulation of canonical NF-kappaB signal transduction / in utero embryonic development / membrane raft / apical plasma membrane / Golgi membrane / negative regulation of gene expression / signaling receptor binding / focal adhesion / intracellular membrane-bounded organelle / 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: 3.7 Å | |||||||||
Authors | Lee HJ / Cha HJ / Jeong H / Lee SN / Lee CW / Woo JS | |||||||||
Funding support | Korea, Republic Of, 1 items
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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 |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33397.map.gz | 48.4 MB | EMDB map data format | |
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Header (meta data) | emd-33397-v30.xml emd-33397.xml | 14 KB 14 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_33397_fsc.xml | 9.1 KB | Display | FSC data file |
Images | emd_33397.png | 8.8 KB | ||
Others | emd_33397_half_map_1.map.gz emd_33397_half_map_2.map.gz | 48.6 MB 48.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33397 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33397 | 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 (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_33397.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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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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Annotation | half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map
File | emd_33397_half_map_2.map | ||||||||||||
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Annotation | half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-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: 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: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 29.396547 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 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.9 µm |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 72.42 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |