+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36465 | |||||||||
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Title | structure of human sodium-calciumexchanger NCX1 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | sodium/calcium exchanger / membrane protein / 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 / cell communication by electrical coupling involved in cardiac conduction / negative regulation of protein serine/threonine kinase activity ...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 / cell communication by electrical coupling involved in cardiac conduction / 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 / relaxation of cardiac muscle / calcium ion transmembrane import into cytosol / Reduction of cytosolic Ca++ levels / ankyrin binding / negative regulation of cytosolic calcium ion concentration / cellular response to caffeine / calcium ion import across plasma membrane / positive regulation of the force of heart contraction / intercalated disc / regulation of cardiac conduction / sodium ion transmembrane transport / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / positive regulation of bone mineralization / calcium ion homeostasis / monoatomic ion transport / muscle contraction / cardiac muscle contraction / axon terminus / Ion homeostasis / T-tubule / response to muscle stretch / cytoskeletal protein binding / regulation of heart rate / cell periphery / calcium ion transmembrane transport / cellular response to reactive oxygen species / sarcolemma / Z disc / intracellular calcium ion homeostasis / regulation of gene expression / transmembrane transporter binding / postsynapse / calmodulin binding / postsynaptic density / axon / neuronal cell body / synapse / dendrite / calcium ion binding / nucleoplasm / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Dong Y / Zhao Y | |||||||||
Funding support | China, 2 items
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Citation | Journal: EMBO J / Year: 2024 Title: Structural insight into the allosteric inhibition of human sodium-calcium exchanger NCX1 by XIP and SEA0400. Authors: Yanli Dong / Zhuoya Yu / Yue Li / Bo Huang / Qinru Bai / Yiwei Gao / Qihao Chen / Na Li / Lingli He / Yan Zhao / Abstract: Sodium-calcium exchanger proteins influence calcium homeostasis in many cell types and participate in a wide range of physiological and pathological processes. Here, we elucidate the cryo-EM ...Sodium-calcium exchanger proteins influence calcium homeostasis in many cell types and participate in a wide range of physiological and pathological processes. Here, we elucidate the cryo-EM structure of the human Na/Ca exchanger NCX1.3 in the presence of a specific inhibitor, SEA0400. Conserved ion-coordinating residues are exposed on the cytoplasmic face of NCX1.3, indicating that the observed structure is stabilized in an inward-facing conformation. We show how regulatory calcium-binding domains (CBDs) assemble with the ion-translocation transmembrane domain (TMD). The exchanger-inhibitory peptide (XIP) is trapped within a groove between the TMD and CBD2 and predicted to clash with gating helices TMs at the outward-facing state, thus hindering conformational transition and promoting inactivation of the transporter. A bound SEA0400 molecule stiffens helix TM2ab and affects conformational rearrangements of TM2ab that are associated with the ion-exchange reaction, thus allosterically attenuating Ca-uptake activity of NCX1.3. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_36465.map.gz | 117.8 MB | EMDB map data format | |
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Header (meta data) | emd-36465-v30.xml emd-36465.xml | 14.7 KB 14.7 KB | Display Display | EMDB header |
Images | emd_36465.png | 87.8 KB | ||
Filedesc metadata | emd-36465.cif.gz | 5.8 KB | ||
Others | emd_36465_half_map_1.map.gz emd_36465_half_map_2.map.gz | 115.9 MB 115.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36465 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36465 | HTTPS FTP |
-Validation report
Summary document | emd_36465_validation.pdf.gz | 770.2 KB | Display | EMDB validaton report |
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Full document | emd_36465_full_validation.pdf.gz | 769.8 KB | Display | |
Data in XML | emd_36465_validation.xml.gz | 13.9 KB | Display | |
Data in CIF | emd_36465_validation.cif.gz | 16.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36465 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36465 | HTTPS FTP |
-Related structure data
Related structure data | 8jp0MC 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_36465.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.82 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_36465_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36465_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Human sodium/calcium exchenger 1(NCX1), monomer
Entire | Name: Human sodium/calcium exchenger 1(NCX1), monomer |
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Components |
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-Supramolecule #1: Human sodium/calcium exchenger 1(NCX1), monomer
Supramolecule | Name: Human sodium/calcium exchenger 1(NCX1), monomer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Sodium/calcium exchanger 1
Macromolecule | Name: Sodium/calcium exchanger 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 104.794266 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MYNMRRLSLS PTFSMGFHLL VTVSLLFSHV DHVIAETEME GEGNETGECT GSYYCKKGVI LPIWEPQDPS FGDKIARATV YFVAMVYMF LGVSIIADRF MSSIEVITSQ EKEITIKKPN GETTKTTVRI WNETVSNLTL MALGSSAPEI LLSVIEVCGH N FTAGDLGP ...String: MYNMRRLSLS PTFSMGFHLL VTVSLLFSHV DHVIAETEME GEGNETGECT GSYYCKKGVI LPIWEPQDPS FGDKIARATV YFVAMVYMF LGVSIIADRF MSSIEVITSQ EKEITIKKPN GETTKTTVRI WNETVSNLTL MALGSSAPEI LLSVIEVCGH N FTAGDLGP STIVGSAAFN MFIIIALCVY VVPDGETRKI KHLRVFFVTA AWSIFAYTWL YIILSVISPG VVEVWEGLLT FF FFPICVV FAWVADRRLL FYKYVYKRYR AGKQRGMIIE HEGDRPSSKT EIEMDGKVVN SHVENFLDGA LVLEVDERDQ DDE EARREM ARILKELKQK HPDKEIEQLI ELANYQVLSQ QQKSRAFYRI QATRLMTGAG NILKRHAADQ ARKAVSMHEV NTEV TENDP VSKIFFEQGT YQCLENCGTV ALTIIRRGGD LTNTVFVDFR TEDGTANAGS DYEFTEGTVV FKPGDTQKEI RVGII DDDI FEEDENFLVH LSNVKVSSEA SEDGILEANH VSTLACLGSP STATVTIFDD DHAGIFTFEE PVTHVSESIG IMEVKV LRT SGARGNVIVP YKTIEGTARG GGEDFEDTCG ELEFQNDEIV KIITIRIFDR EEYEKECSFS LVLEEPKWIR RGMKGGF TI TDEYDDKQPL TSKEEEERRI AEMGRPILGE HTKLEVIIEE SYEFKSTVDK LIKKTNLALV VGTNSWREQF IEAITVSA G EDDDDDECGE EKLPSCFDYV MHFLTVFWKV LFAFVPPTEY WNGWACFIVS ILMIGLLTAF IGDLASHFGC TIGLKDSVT AVVFVALGTS VPDTFASKVA ATQDQYADAS IGNVTGSNAV NVFLGIGVAW SIAAIYHAAN GEQFKVSPGT LAFSVTLFTI FAFINVGVL LYRRRPEIGG ELGGPRTAKL LTSCLFVLLW LLYIFFSSLE AYCHIKGF UniProtKB: Sodium/calcium exchanger 1 |
-Macromolecule #2: 2-{4-[(2,5-difluorophenyl)methoxy]phenoxy}-5-ethoxyaniline
Macromolecule | Name: 2-{4-[(2,5-difluorophenyl)methoxy]phenoxy}-5-ethoxyaniline type: ligand / ID: 2 / Number of copies: 1 / Formula: EKY |
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Molecular weight | Theoretical: 371.377 Da |
Chemical component information | ChemComp-EKY: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k 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: 22.0 µm / Nominal defocus min: 12.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 177782 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |