[English] 日本語
Yorodumi
- PDB-6baa: Cryo-EM structure of the pancreatic beta-cell KATP channel bound ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6baa
TitleCryo-EM structure of the pancreatic beta-cell KATP channel bound to ATP and glibenclamide
Components
  • ATP-binding cassette sub-family C member 8
  • ATP-sensitive inward rectifier potassium channel 11
KeywordsMETAL TRANSPORT / KATP / SUR1 / Kir6.2 / sulfonylurea receptor
Function / homology
Function and homology information


ATP sensitive Potassium channels / Ion homeostasis / Regulation of insulin secretion / ABC-family proteins mediated transport / inward rectifying potassium channel / ATP-activated inward rectifier potassium channel activity / sulfonylurea receptor activity / cell body fiber / inward rectifier potassium channel activity / positive regulation of cation channel activity ...ATP sensitive Potassium channels / Ion homeostasis / Regulation of insulin secretion / ABC-family proteins mediated transport / inward rectifying potassium channel / ATP-activated inward rectifier potassium channel activity / sulfonylurea receptor activity / cell body fiber / inward rectifier potassium channel activity / positive regulation of cation channel activity / response to ATP / potassium ion import across plasma membrane / ankyrin binding / axolemma / nervous system process / potassium channel activity / intercalated disc / response to testosterone / T-tubule / ATPase-coupled transmembrane transporter activity / negative regulation of insulin secretion / regulation of membrane potential / response to ischemia / heat shock protein binding / acrosomal vesicle / potassium ion transport / cellular response to glucose stimulus / sarcolemma / positive regulation of protein localization to plasma membrane / nuclear envelope / cellular response to nicotine / glucose metabolic process / cellular response to tumor necrosis factor / myelin sheath / ion channel binding / response to estradiol / response to drug / protein C-terminus binding / endosome / ATPase activity / intracellular membrane-bounded organelle / neuronal cell body / endoplasmic reticulum / mitochondrion / integral component of membrane / ATP binding / plasma membrane / cytosol
Sulphonylurea receptor / Potassium channel, inwardly rectifying, Kir, cytoplasmic / Potassium channel, inwardly rectifying, Kir / ABC transporter, conserved site / P-loop containing nucleoside triphosphate hydrolase / ABC transporter type 1, transmembrane domain / ABC transporter type 1, transmembrane domain superfamily / AAA+ ATPase domain / Potassium channel, inwardly rectifying, transmembrane domain / ABC transporter-like ...Sulphonylurea receptor / Potassium channel, inwardly rectifying, Kir, cytoplasmic / Potassium channel, inwardly rectifying, Kir / ABC transporter, conserved site / P-loop containing nucleoside triphosphate hydrolase / ABC transporter type 1, transmembrane domain / ABC transporter type 1, transmembrane domain superfamily / AAA+ ATPase domain / Potassium channel, inwardly rectifying, transmembrane domain / ABC transporter-like / ATP-binding cassette subfamily C member 8 / Potassium channel, inwardly rectifying, Kir6.2 / Inward rectifier potassium channel, C-terminal / ABC transporter / Immunoglobulin E-set / ABC transporter integral membrane type-1 fused domain profile. / ABC transporter transmembrane region / Inward rectifier potassium channel transmembrane domain / Inward rectifier potassium channel C-terminal domain / ABC transporters family signature. / ATP-binding cassette, ABC transporter-type domain profile.
ATP-sensitive inward rectifier potassium channel 11 / ATP-binding cassette sub-family C member 8
Biological speciesRattus norvegicus (Norway rat)
Cricetus cricetus (black-bellied hamster)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.63 Å
AuthorsMartin, G.M. / Yoshioka, C. / Shyng, S.L.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease United States
CitationJournal: Elife / Year: 2017
Title: Anti-diabetic drug binding site in a mammalian K channel revealed by Cryo-EM.
Authors: Gregory M Martin / Balamurugan Kandasamy / Frank DiMaio / Craig Yoshioka / Show-Ling Shyng /
Abstract: Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic K channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been ...Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic K channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been extensively investigated, yet it remains unclear where the drug binding pocket resides. Here, we present a cryo-EM structure of a hamster SUR1/rat Kir6.2 channel bound to a high-affinity sulfonylurea drug glibenclamide and ATP at 3.63 Å resolution, which reveals unprecedented details of the ATP and glibenclamide binding sites. Importantly, the structure shows for the first time that glibenclamide is lodged in the transmembrane bundle of the SUR1-ABC core connected to the first nucleotide binding domain near the inner leaflet of the lipid bilayer. Mutation of residues predicted to interact with glibenclamide in our model led to reduced sensitivity to glibenclamide. Our structure provides novel mechanistic insights of how sulfonylureas and ATP interact with the K channel complex to inhibit channel activity.
Validation Report
SummaryFull reportAbout validation report
History
DepositionOct 12, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 1, 2017Provider: repository / Type: Initial release
Revision 1.1Feb 28, 2018Group: Database references / Category: citation / Item: _citation.title
Revision 1.2Mar 28, 2018Group: Data collection / Database references / Category: citation / Item: _citation.title

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-7073
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: ATP-sensitive inward rectifier potassium channel 11
B: ATP-sensitive inward rectifier potassium channel 11
C: ATP-sensitive inward rectifier potassium channel 11
D: ATP-sensitive inward rectifier potassium channel 11
E: ATP-binding cassette sub-family C member 8
F: ATP-binding cassette sub-family C member 8
G: ATP-binding cassette sub-family C member 8
H: ATP-binding cassette sub-family C member 8
hetero molecules


Theoretical massNumber of molelcules
Total (without water)887,92216
Polymers883,9178
Non-polymers4,0058
Water0
1


TypeNameSymmetry operationNumber
identity operation1_5551
Buried area41760 Å2
ΔGint-312 kcal/mol
Surface area299500 Å2

-
Components

#1: Protein/peptide
ATP-sensitive inward rectifier potassium channel 11 / BIR / Inward rectifier K(+) channel Kir6.2 / Potassium channel / inwardly rectifying subfamily J member 11


Mass: 43645.719 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Kcnj11 / Cell line (production host): INS-1 / Production host: Rattus norvegicus (Norway rat) / References: UniProt: P70673
#2: Protein/peptide
ATP-binding cassette sub-family C member 8 / Sulfonylurea receptor 1


Mass: 177333.578 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Cricetus cricetus (black-bellied hamster)
Gene: ABCC8, SUR / Production host: Rattus norvegicus (Norway rat) / References: UniProt: Q09427
#3: Chemical
ChemComp-ATP / ADENOSINE-5'-TRIPHOSPHATE


Mass: 507.181 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C10H16N5O13P3 / Adenosine triphosphate / Comment: ATP (energy-carrying molecule) *YM
#4: Chemical
ChemComp-GBM / 5-chloro-N-(2-{4-[(cyclohexylcarbamoyl)sulfamoyl]phenyl}ethyl)-2-methoxybenzamide / Glibenclamide, Glyburide


Mass: 494.004 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C23H28ClN3O5S / Glibenclamide

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

Component

Source: RECOMBINANT / Type: COMPLEX

IDNameEntity IDParent-ID
1Pancreatic beta-cell ATP-sensitive K+ channel (KATP)1, 20
2ATP-sensitive K+ channel subunit Kir6.211
3ATP-binding cassette sub-family C member 821
Molecular weightValue: 0.95 MDa / Experimental value: NO
Source (natural)

Entity assembly-ID: 1

IDOrganismNcbi tax-ID
1Rattus norvegicus (Norway rat)10116
2Cricetus cricetus (black-bellied hamster)10034
Source (recombinant)

Entity assembly-ID: 1 / Ncbi tax-ID: 10116 / Organism: Rattus norvegicus (Norway rat)

ID
1
2
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy
Image recordingElectron dose: 40 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C4 (4 fold cyclic)
3D reconstructionResolution: 3.63 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 59417 / Symmetry type: POINT

+
About Yorodumi

-
News

-
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force. (see PDBe EMDB page)
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.: Q: What is "EMD"? / ID/Accession-code notation in Yorodumi/EM Navigator

External links: EMDB at PDBe / Contact to PDBj

-
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary. This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated. See below links for details.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software). Now, EM Navigator and Yorodumi are based on the updated data.

External links: wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.: Omokage search

+
Sep 15, 2016. EM Navigator & Yorodumi renewed

EM Navigator & Yorodumi renewed

  • New versions of EM Navigator and Yorodumi started

Related info.: Changes in new EM Navigator and Yorodumi

+
Aug 31, 2016. New EM Navigator & Yorodumi

New EM Navigator & Yorodumi

  • In 15th Sep 2016, the development versions of EM Navigator and Yorodumi will replace the official versions.
  • Current version will continue as 'legacy version' for some time.

Related info.: Changes in new EM Navigator and Yorodumi / EM Navigator / Yorodumi

Read more

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.

Related info.: EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more