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Yorodumi- PDB-7xqj: Hemichannel-focused structure of C-terminal truncated connexin43/... -
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-Basic information
Entry | Database: PDB / ID: 7xqj | ||||||
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Title | Hemichannel-focused structure of C-terminal truncated connexin43/Cx43/GJA1 gap junction intercellular channel in POPE nanodiscs (PLN conformation) | ||||||
Components | Gap junction alpha-1 protein | ||||||
Keywords | MEMBRANE PROTEIN / Cx43 / Connexin / Gap junction channel / Gating mechanism | ||||||
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 / 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 / cell junction / protein localization / cell-cell signaling / heart development / positive regulation of cold-induced thermogenesis / positive regulation of canonical NF-kappaB signal transduction / scaffold protein binding / spermatogenesis / in utero embryonic development / apical plasma membrane / membrane raft / Golgi membrane / negative regulation of gene expression / intracellular membrane-bounded organelle / focal adhesion / signaling receptor binding / 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: 4 Å | ||||||
Authors | Lee, H.J. / Cha, H.J. / Jeong, H. / Lee, S.N. / Lee, C.W. / Woo, J.S. | ||||||
Funding support | Korea, Republic Of, 1items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7xqj.cif.gz | 225.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7xqj.ent.gz | 182 KB | Display | PDB format |
PDBx/mmJSON format | 7xqj.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7xqj_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7xqj_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7xqj_validation.xml.gz | 45.6 KB | Display | |
Data in CIF | 7xqj_validation.cif.gz | 64.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xq/7xqj ftp://data.pdbj.org/pub/pdb/validation_reports/xq/7xqj | HTTPS FTP |
-Related structure data
Related structure data | 33398MC 7f92C 7f93C 7f94C 7xq9C 7xqbC 7xqdC 7xqfC 7xqgC 7xqhC 7xqiC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 29396.547 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GJA1, GJAL / 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: Dodecameric complex of C-terminal deletion mutant of human Cx43/GJA1 (Cx43-M257) in lipid nanodiscs (POPE) Type: COMPLEX Details: Hemichannel of Human Cx43-M257 gap junction channel with pore-lining NTH conformation Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | 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: 2400 nm / Nominal defocus min: 900 nm |
Image recording | Electron dose: 72.42 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 35388 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Stereochemistry target values: CDL v1.2 | ||||||||||||||||||||||||
Refine LS restraints |
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