+Open data
-Basic information
Entry | Database: PDB / ID: 7vlu | ||||||||||||
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Title | Structure of SUR2A in complex with Mg-ATP/ADP and P1075 | ||||||||||||
Components | ATP-binding cassette sub-family C member 9 | ||||||||||||
Keywords | MEMBRANE PROTEIN / SUR2A / ABC transporter / P1075 | ||||||||||||
Function / homology | Function and homology information substrate-dependent cell migration, cell contraction / ATP sensitive Potassium channels / ABC-family proteins mediated transport / circulatory system development / inward rectifying potassium channel / sulfonylurea receptor activity / cardiac conduction / coronary vasculature development / ATPase-coupled monoatomic cation transmembrane transporter activity / cardiac muscle cell contraction ...substrate-dependent cell migration, cell contraction / ATP sensitive Potassium channels / ABC-family proteins mediated transport / circulatory system development / inward rectifying potassium channel / sulfonylurea receptor activity / cardiac conduction / coronary vasculature development / ATPase-coupled monoatomic cation transmembrane transporter activity / cardiac muscle cell contraction / inorganic cation transmembrane transport / syntaxin binding / Ion homeostasis / response to ATP / heterocyclic compound binding / blood vessel development / potassium ion import across plasma membrane / action potential / monoatomic cation transmembrane transport / ATPase-coupled transmembrane transporter activity / potassium channel regulator activity / ABC-type transporter activity / heart morphogenesis / potassium ion transmembrane transport / T-tubule / negative regulation of blood pressure / sarcomere / potassium ion transport / acrosomal vesicle / regulation of blood pressure / transmembrane transport / fibroblast proliferation / defense response to virus / transmembrane transporter binding / response to xenobiotic stimulus / ATP hydrolysis activity / ATP binding / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Rattus norvegicus (Norway rat) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||
Authors | Chen, L. / Ding, D. | ||||||||||||
Funding support | China, 3items
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Citation | Journal: Nat Commun / Year: 2022 Title: Structural identification of vasodilator binding sites on the SUR2 subunit. Authors: Dian Ding / Jing-Xiang Wu / Xinli Duan / Songling Ma / Lipeng Lai / Lei Chen / Abstract: ATP-sensitive potassium channels (K), composed of Kir6 and SUR subunits, convert the metabolic status of the cell into electrical signals. Pharmacological activation of SUR2- containing K channels by ...ATP-sensitive potassium channels (K), composed of Kir6 and SUR subunits, convert the metabolic status of the cell into electrical signals. Pharmacological activation of SUR2- containing K channels by class of small molecule drugs known as K openers leads to hyperpolarization of excitable cells and to vasodilation. Thus, K openers could be used to treat cardiovascular diseases. However, where these vasodilators bind to K and how they activate the channel remains elusive. Here, we present cryo-EM structures of SUR2A and SUR2B subunits in complex with Mg-nucleotides and P1075 or levcromakalim, two chemically distinct K openers that are specific to SUR2. Both P1075 and levcromakalim bind to a common site in the transmembrane domain (TMD) of the SUR2 subunit, which is between TMD1 and TMD2 and is embraced by TM10, TM11, TM12, TM14, and TM17. These K openers synergize with Mg-nucleotides to stabilize SUR2 in the NBD-dimerized occluded state to activate the channel. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7vlu.cif.gz | 246.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7vlu.ent.gz | 187.6 KB | Display | PDB format |
PDBx/mmJSON format | 7vlu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7vlu_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 7vlu_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 7vlu_validation.xml.gz | 39.8 KB | Display | |
Data in CIF | 7vlu_validation.cif.gz | 58.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vl/7vlu ftp://data.pdbj.org/pub/pdb/validation_reports/vl/7vlu | HTTPS FTP |
-Related structure data
Related structure data | 32027MC 7vlrC 7vlsC 7vltC 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
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 174300.422 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Abcc9, Sur2 / Production host: Homo sapiens (human) / References: UniProt: Q63563 |
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-Non-polymers , 5 types, 6 molecules
#2: Chemical | ChemComp-Y01 / | ||||
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#3: Chemical | ChemComp-ADP / | ||||
#4: Chemical | #5: Chemical | ChemComp-ATP / | #6: Chemical | ChemComp-ESV / | |
-Details
Has ligand of interest | Y |
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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: ATP-binding cassette sub-family C member 9, isoform A / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 174 kDa/nm / Experimental value: NO |
Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Source (recombinant) | Organism: Homo sapiens (human) |
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: 1800 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 52 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software | Name: cryoSPARC / Version: 3.1.0 / Category: 3D reconstruction |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 104350 / Symmetry type: POINT |