+Open data
-Basic information
Entry | Database: PDB / ID: 8jp0 | |||||||||
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Title | structure of human sodium-calciumexchanger NCX1 | |||||||||
Components | Sodium/calcium exchanger 1 | |||||||||
Keywords | TRANSPORT PROTEIN / sodium/calcium exchanger / membrane 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 / cardiac muscle contraction / axon terminus / muscle contraction / Ion homeostasis / T-tubule / response to muscle stretch / cytoskeletal protein binding / regulation of heart rate / cell periphery / calcium ion transmembrane transport / sarcolemma / Z disc / cellular response to reactive oxygen species / intracellular calcium ion homeostasis / regulation of gene expression / postsynapse / transmembrane transporter binding / postsynaptic density / calmodulin binding / axon / neuronal cell body / dendrite / synapse / calcium ion binding / nucleoplasm / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Dong, Y. / Zhao, Y. | |||||||||
Funding support | China, 2items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8jp0.cif.gz | 139.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8jp0.ent.gz | 105.9 KB | Display | PDB format |
PDBx/mmJSON format | 8jp0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8jp0_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8jp0_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8jp0_validation.xml.gz | 34.5 KB | Display | |
Data in CIF | 8jp0_validation.cif.gz | 49 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jp/8jp0 ftp://data.pdbj.org/pub/pdb/validation_reports/jp/8jp0 | HTTPS FTP |
-Related structure data
Related structure data | 36465MC 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: 104794.266 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SLC8A1, CNC, NCX1 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P32418 |
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#2: Chemical | ChemComp-EKY / |
Has ligand of interest | Y |
-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: Human sodium/calcium exchenger 1(NCX1), monomer / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: HEK293 |
Buffer solution | pH: 7.5 |
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: 22000 nm / Nominal defocus min: 12000 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 177782 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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