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Yorodumi- PDB-7y1l: Structure of SUR2B in complex with Mg-ATP and repaglinide in the ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7y1l | ||||||||||||
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Title | Structure of SUR2B in complex with Mg-ATP and repaglinide in the inward-facing conformation | ||||||||||||
Components | Isoform SUR2B of ATP-binding cassette sub-family C member 9 | ||||||||||||
Keywords | MEMBRANE PROTEIN / SUR2B / ABC transporter / repaglinide | ||||||||||||
Function / homology | Function and homology information substrate-dependent cell migration, cell contraction / ATP sensitive Potassium channels / ABC-family proteins mediated transport / inward rectifying potassium channel / sulfonylurea receptor activity / circulatory system development / 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 / inward rectifying potassium channel / sulfonylurea receptor activity / circulatory system development / cardiac conduction / coronary vasculature development / ATPase-coupled monoatomic cation transmembrane transporter activity / cardiac muscle cell contraction / inorganic cation transmembrane transport / syntaxin binding / heterocyclic compound binding / Ion homeostasis / response to ATP / action potential / blood vessel development / potassium ion import across plasma membrane / monoatomic cation transmembrane transport / ATPase-coupled transmembrane transporter activity / ABC-type transporter activity / potassium channel regulator activity / heart morphogenesis / potassium ion transmembrane transport / T-tubule / negative regulation of blood pressure / sarcomere / acrosomal vesicle / potassium ion transport / transmembrane transport / regulation of blood pressure / 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: 3.73 Å | ||||||||||||
Authors | Chen, L. / Ding, D. / Hou, T. | ||||||||||||
Funding support | China, 3items
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Citation | Journal: Nat Commun / Year: 2023 Title: The inhibition mechanism of the SUR2A-containing K channel by a regulatory helix. Authors: Dian Ding / Tianyi Hou / Miao Wei / Jing-Xiang Wu / Lei Chen / Abstract: K channels are metabolic sensors for intracellular ATP/ADP ratios, play essential roles in many physiological processes, and are implicated in a spectrum of pathological conditions. SUR2A-containing ...K channels are metabolic sensors for intracellular ATP/ADP ratios, play essential roles in many physiological processes, and are implicated in a spectrum of pathological conditions. SUR2A-containing K channels differ from other subtypes in their sensitivity to Mg-ADP activation. However, the underlying structural mechanism remains poorly understood. Here we present a series of cryo-EM structures of SUR2A in the presence of different combinations of Mg-nucleotides and the allosteric inhibitor repaglinide. These structures uncover regulatory helix (R helix) on the NBD1-TMD2 linker, which wedges between NBD1 and NBD2. R helix stabilizes SUR2A in the NBD-separated conformation to inhibit channel activation. The competitive binding of Mg-ADP with Mg-ATP to NBD2 mobilizes the R helix to relieve such inhibition, allowing channel activation. The structures of SUR2B in similar conditions suggest that the C-terminal 42 residues of SUR2B enhance the structural dynamics of NBD2 and facilitate the dissociation of the R helix and the binding of Mg-ADP to NBD2, promoting NBD dimerization and subsequent channel activation. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
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PDBx/mmCIF format | 7y1l.cif.gz | 221.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7y1l.ent.gz | 167.5 KB | Display | PDB format |
PDBx/mmJSON format | 7y1l.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7y1l_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 7y1l_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 7y1l_validation.xml.gz | 44 KB | Display | |
Data in CIF | 7y1l_validation.cif.gz | 63.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/y1/7y1l ftp://data.pdbj.org/pub/pdb/validation_reports/y1/7y1l | HTTPS FTP |
-Related structure data
Related structure data | 33565MC 7y1jC 7y1kC 7y1mC 7y1nC 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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-Components
#1: Protein | Mass: 174488.562 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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#2: Chemical | #3: Chemical | #4: Chemical | ChemComp-BJX / | 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: ATP-binding cassette sub-family C member 9, isoform B / 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: 2000 nm / Nominal defocus min: 1800 nm |
Image recording | Electron dose: 52 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software | Name: cryoSPARC / Category: 3D reconstruction |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction | Resolution: 3.73 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 60550 / Symmetry type: POINT |