+Open data
-Basic information
Entry | Database: PDB / ID: 7dsv | ||||||
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Title | Structure of a human NHE1-CHP1 complex under pH 6.5 | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / Transporter | ||||||
Function / homology | Function and homology information positive regulation of sodium:proton antiporter activity / sodium:proton antiporter activity involved in regulation of cardiac muscle cell membrane potential / cation-transporting ATPase complex / Sodium/Proton exchangers / negative regulation of phosphatase activity / regulation of the force of heart contraction by cardiac conduction / transporter complex / positive regulation of calcium:sodium antiporter activity / positive regulation of protein glycosylation / Hyaluronan uptake and degradation ...positive regulation of sodium:proton antiporter activity / sodium:proton antiporter activity involved in regulation of cardiac muscle cell membrane potential / cation-transporting ATPase complex / Sodium/Proton exchangers / negative regulation of phosphatase activity / regulation of the force of heart contraction by cardiac conduction / transporter complex / positive regulation of calcium:sodium antiporter activity / positive regulation of protein glycosylation / Hyaluronan uptake and degradation / membrane docking / regulation of cardiac muscle cell membrane potential / cellular response to electrical stimulus / positive regulation of phospholipid biosynthetic process / negative regulation of protein autophosphorylation / potassium:proton antiporter activity / sodium:proton antiporter activity / positive regulation of action potential / positive regulation of protein transport / maintenance of cell polarity / positive regulation of calcineurin-NFAT signaling cascade / regulation of pH / sodium ion export across plasma membrane / cardiac muscle cell differentiation / cellular response to acidic pH / membrane organization / sodium ion import across plasma membrane / protein phosphatase 2B binding / intracellular sodium ion homeostasis / microtubule bundle formation / response to acidic pH / regulation of stress fiber assembly / cardiac muscle cell contraction / regulation of cardiac muscle contraction by calcium ion signaling / positive regulation of mitochondrial membrane permeability / cellular response to cold / negative regulation of calcineurin-NFAT signaling cascade / cellular response to antibiotic / regulation of focal adhesion assembly / negative regulation of NF-kappaB transcription factor activity / negative regulation of protein import into nucleus / small GTPase-mediated signal transduction / positive regulation of cardiac muscle hypertrophy / protein kinase inhibitor activity / positive regulation of the force of heart contraction / endoplasmic reticulum-Golgi intermediate compartment / cellular response to organic cyclic compound / intercalated disc / positive regulation of protein targeting to membrane / potassium channel regulator activity / monoatomic ion transport / cytoplasmic microtubule organization / transport vesicle / potassium ion transmembrane transport / negative regulation of protein ubiquitination / T-tubule / cellular response to epinephrine stimulus / phosphatidylinositol-4,5-bisphosphate binding / response to muscle stretch / protein export from nucleus / proton transmembrane transport / potassium ion transport / negative regulation of protein phosphorylation / stem cell differentiation / regulation of intracellular pH / kinase binding / negative regulation of protein kinase activity / cellular response to mechanical stimulus / cellular response to insulin stimulus / phospholipid binding / calcium-dependent protein binding / microtubule cytoskeleton / cell migration / lamellipodium / protein complex oligomerization / cellular response to hypoxia / positive regulation of cell growth / protein-macromolecule adaptor activity / basolateral plasma membrane / microtubule binding / molecular adaptor activity / membrane fusion / calmodulin binding / protein stabilization / apical plasma membrane / membrane raft / positive regulation of apoptotic process / Golgi membrane / focal adhesion / calcium ion binding / negative regulation of apoptotic process / perinuclear region of cytoplasm / cell surface / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / mitochondrion / extracellular exosome / nucleoplasm / identical protein binding / membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||
Authors | Dong, Y. / Gao, Y. / Li, B. / Zhang, X.C. / Zhao, Y. | ||||||
Citation | Journal: Nat Commun / Year: 2021 Title: Structure and mechanism of the human NHE1-CHP1 complex. Authors: Yanli Dong / Yiwei Gao / Alina Ilie / DuSik Kim / Annie Boucher / Bin Li / Xuejun C Zhang / John Orlowski / Yan Zhao / Abstract: Sodium/proton exchanger 1 (NHE1) is an electroneutral secondary active transporter present on the plasma membrane of most mammalian cells and plays critical roles in regulating intracellular pH and ...Sodium/proton exchanger 1 (NHE1) is an electroneutral secondary active transporter present on the plasma membrane of most mammalian cells and plays critical roles in regulating intracellular pH and volume homeostasis. Calcineurin B-homologous protein 1 (CHP1) is an obligate binding partner that promotes NHE1 biosynthetic maturation, cell surface expression and pH-sensitivity. Dysfunctions of either protein are associated with neurological disorders. Here, we elucidate structures of the human NHE1-CHP1 complex in both inward- and inhibitor (cariporide)-bound outward-facing conformations. We find that NHE1 assembles as a symmetrical homodimer, with each subunit undergoing an elevator-like conformational change during cation exchange. The cryo-EM map reveals the binding site for the NHE1 inhibitor cariporide, illustrating how inhibitors block transport activity. The CHP1 molecule differentially associates with these two conformational states of each NHE1 monomer, and this association difference probably underlies the regulation of NHE1 pH-sensitivity by CHP1. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7dsv.cif.gz | 228.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7dsv.ent.gz | 172.5 KB | Display | PDB format |
PDBx/mmJSON format | 7dsv.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7dsv_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 7dsv_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 7dsv_validation.xml.gz | 44 KB | Display | |
Data in CIF | 7dsv_validation.cif.gz | 66.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ds/7dsv ftp://data.pdbj.org/pub/pdb/validation_reports/ds/7dsv | HTTPS FTP |
-Related structure data
Related structure data | 30847MC 7dswC 7dsxC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 52893.367 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SLC9A1, APNH1, NHE1 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P19634 #2: Protein | Mass: 21369.830 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CHP1, CHP / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q99653 #3: Chemical | ChemComp-LBN / Has ligand of interest | N | |
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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
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Molecular weight |
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 6.5 | ||||||||||||||||||||||||||||
Specimen | Conc.: 6 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: The NHE1-CHP1 complex was reconstituted into lipid nanodiscs. | ||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil | ||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 13000 X / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2205 |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
Image scans | Width: 3838 / Height: 3710 / Movie frames/image: 32 / Used frames/image: 1-32 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 100503 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL |