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Yorodumi- EMDB-40460: Cryo-EM map of human cardiac sodium calcium exchanger NCX1 in apo... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-40460 | ||||||||||||
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Title | Cryo-EM map of human cardiac sodium calcium exchanger NCX1 in apo, inactivated state (group I in the presence of 0.5mM Ca2+) | ||||||||||||
Map data | |||||||||||||
Sample |
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Keywords | Na/Ca exchanger / sodium calcium exchanger / TRANSPORT PROTEIN | ||||||||||||
Function / homology | Function and homology information relaxation of smooth muscle / vascular associated smooth muscle contraction / calcium ion export / regulation of cell communication by electrical coupling / calcium:sodium antiporter activity / membrane depolarization during cardiac muscle cell action potential / regulation of the force of heart contraction / sodium ion export across plasma membrane / negative regulation of protein serine/threonine kinase activity / sodium ion import across plasma membrane ...relaxation of smooth muscle / vascular associated smooth muscle contraction / calcium ion export / regulation of cell communication by electrical coupling / calcium:sodium antiporter activity / membrane depolarization during cardiac muscle cell action potential / regulation of the force of heart contraction / sodium ion export across plasma membrane / negative regulation of protein serine/threonine kinase activity / sodium ion import across plasma membrane / intracellular sodium ion homeostasis / calcium ion import / regulation of cardiac muscle contraction by calcium ion signaling / cardiac muscle cell development / calcium ion transport into cytosol / Sodium/Calcium exchangers / calcium ion transmembrane import into cytosol / relaxation of cardiac muscle / cell communication by electrical coupling involved in cardiac conduction / Reduction of cytosolic Ca++ levels / ankyrin binding / negative regulation of cytosolic calcium ion concentration / cellular response to caffeine / positive regulation of the force of heart contraction / intercalated disc / sodium ion transmembrane transport / calcium ion import across plasma membrane / regulation of cardiac conduction / calcium ion homeostasis / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / positive regulation of bone mineralization / monoatomic ion transport / cardiac muscle contraction / axon terminus / Ion homeostasis / T-tubule / cytoskeletal protein binding / response to muscle stretch / regulation of heart rate / muscle contraction / cell periphery / calcium ion transmembrane transport / sarcolemma / Z disc / cellular response to reactive oxygen species / intracellular calcium ion homeostasis / postsynapse / regulation of gene expression / transmembrane transporter binding / postsynaptic density / calmodulin binding / axon / neuronal cell body / synapse / calcium ion binding / dendrite / nucleoplasm / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | ||||||||||||
Authors | Xue J / Jiang Y | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: Nat Commun / Year: 2023 Title: Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1. Authors: Jing Xue / Weizhong Zeng / Yan Han / Scott John / Michela Ottolia / Youxing Jiang / Abstract: Na/Ca exchangers (NCX) transport Ca in or out of cells in exchange for Na. They are ubiquitously expressed and play an essential role in maintaining cytosolic Ca homeostasis. Although extensively ...Na/Ca exchangers (NCX) transport Ca in or out of cells in exchange for Na. They are ubiquitously expressed and play an essential role in maintaining cytosolic Ca homeostasis. Although extensively studied, little is known about the global structural arrangement of eukaryotic NCXs and the structural mechanisms underlying their regulation by various cellular cues including cytosolic Na and Ca. Here we present the cryo-EM structures of human cardiac NCX1 in both inactivated and activated states, elucidating key structural elements important for NCX ion exchange function and its modulation by cytosolic Ca and Na. We demonstrate that the interactions between the ion-transporting transmembrane (TM) domain and the cytosolic regulatory domain define the activity of NCX. In the inward-facing state with low cytosolic [Ca], a TM-associated four-stranded β-hub mediates a tight packing between the TM and cytosolic domains, resulting in the formation of a stable inactivation assembly that blocks the TM movement required for ion exchange function. Ca binding to the cytosolic second Ca-binding domain (CBD2) disrupts this inactivation assembly which releases its constraint on the TM domain, yielding an active exchanger. Thus, the current NCX1 structures provide an essential framework for the mechanistic understanding of the ion transport and cellular regulation of NCX family proteins. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_40460.map.gz | 168.1 MB | EMDB map data format | |
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Header (meta data) | emd-40460-v30.xml emd-40460.xml | 15.3 KB 15.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_40460_fsc.xml | 11.9 KB | Display | FSC data file |
Images | emd_40460.png | 67.1 KB | ||
Filedesc metadata | emd-40460.cif.gz | 5.3 KB | ||
Others | emd_40460_half_map_1.map.gz emd_40460_half_map_2.map.gz | 165.4 MB 165.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-40460 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40460 | HTTPS FTP |
-Validation report
Summary document | emd_40460_validation.pdf.gz | 912.1 KB | Display | EMDB validaton report |
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Full document | emd_40460_full_validation.pdf.gz | 911.6 KB | Display | |
Data in XML | emd_40460_validation.xml.gz | 20 KB | Display | |
Data in CIF | emd_40460_validation.cif.gz | 25.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40460 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40460 | HTTPS FTP |
-Related structure data
Related structure data | 8sgjC 8sgtC 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_40460.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_40460_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_40460_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : human cardiac sodium calcium exchanger NCX1 in apo, inactivated s...
Entire | Name: human cardiac sodium calcium exchanger NCX1 in apo, inactivated state ( group I in the presence of 0.5mM Ca2+) and bound Fab fragment |
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Components |
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-Supramolecule #1: human cardiac sodium calcium exchanger NCX1 in apo, inactivated s...
Supramolecule | Name: human cardiac sodium calcium exchanger NCX1 in apo, inactivated state ( group I in the presence of 0.5mM Ca2+) and bound Fab fragment type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: human cardiac sodium calcium exchanger NCX1 in apo, inactivated s...
Supramolecule | Name: human cardiac sodium calcium exchanger NCX1 in apo, inactivated state ( group I in the presence of 0.5mM Ca2+) type: complex / ID: 2 / Parent: 1 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: antibody Fab fragment
Supramolecule | Name: antibody Fab fragment / type: complex / ID: 3 / Parent: 1 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Macromolecule #1: human cardiac sodium calcium exchanger NCX1
Macromolecule | Name: human cardiac sodium calcium exchanger NCX1 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MYNMRRLSLS PTFSMGFHLL VTVSLLFSHV DHVIAETEME GEGNETGECT GSYYCKKGVI LPIWEPQDPS FGDKIARATV YFVAMVYMFL GVSIIADRFM SSIEVITSQE KEITIKKPNG ETTKTTVRIW NETVSNLTLM ALGSSAPEIL LSVIEVCGHN FTAGDLGPST ...String: MYNMRRLSLS PTFSMGFHLL VTVSLLFSHV DHVIAETEME GEGNETGECT GSYYCKKGVI LPIWEPQDPS FGDKIARATV YFVAMVYMFL GVSIIADRFM SSIEVITSQE KEITIKKPNG ETTKTTVRIW NETVSNLTLM ALGSSAPEIL LSVIEVCGHN FTAGDLGPST IVGSAAFNMF IIIALCVYVV PDGETRKIKH LRVFFVTAAW SIFAYTWLYI ILSVISPGVV EVWEGLLTFF FFPICVVFAW VADRRLLFYK YVYKRYRAGK QRGMIIEHEG DRPSSKTEIE MDGKVVNSHV ENFLDGALVL EVDERDQDDE EARREMARIL KELKQKHPDK EIEQLIELAN YQVLSQQQKS RAFYRIQATR LMTGATENDP VSKIFFEQGT YQCLENCGTV ALTIIRRGGD LTNTVFVDFR TEDGTANAGS DYEFTEGTVV FKPGDTQKEI RVGIIDDDIF EEDENFLVHL SNVKVSSEAS EDGILEANHV STLACLGSPS TATVTIFDDD HAGIFTFEEP VTHVSESIGI MEVKVLRTSG ARGNVIVPYK TIEGTARGGG EDFEDTCGEL EFQNDEIVKT ISVKVIDDEE YEKNKTFFLE IGEPRLVEMS EKKALLLNEL GGFTITGKYL FGQPVFRKVH AREHPILSTV ITIADEYDDK QPLTSKEEEE RRIAEMGRPI LGEHTKLEVI IEESYEFKST VDKLIKKTNL ALVVGTNSWR EQFIEAITVS AGEDDDDDEC GEEKLPSCFD YVMHFLTVFW KVLFAFVPPT EYWNGWACFI VSILMIGLLT AFIGDLASHF GCTIGLKDSV TAVVFVALGT SVPDTFASKV AATQDQYADA SIGNVTGSNA VNVFLGIGVA WSIAAIYHAA NGEQFKVSPG TLAFSVTLFT IFAFINVGVL LYRRRPEIGG ELGGPRTAKL LTSCLFVLLW LLYIFFSSLE AYCHIKGF UniProtKB: Sodium/calcium exchanger 1 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-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: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |