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- PDB-7s5v: Human KATP channel in open conformation, focused on SUR -

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Basic information

Entry
Database: PDB / ID: 7s5v
TitleHuman KATP channel in open conformation, focused on SUR
ComponentsATP-binding cassette sub-family C member 8
KeywordsMEMBRANE PROTEIN / ion channel / KATP / ATP-sensitive potassium channel
Function / homology
Function and homology information


negative regulation of neuroblast migration / positive regulation of uterine smooth muscle relaxation / ATP sensitive Potassium channels / Defective ABCC8 can cause hypo- and hyper-glycemias / potassium ion-transporting ATPase complex / positive regulation of tight junction disassembly / negative regulation of low-density lipoprotein particle clearance / negative regulation of blood-brain barrier permeability / ATP-activated inward rectifier potassium channel activity / glutamate secretion, neurotransmission ...negative regulation of neuroblast migration / positive regulation of uterine smooth muscle relaxation / ATP sensitive Potassium channels / Defective ABCC8 can cause hypo- and hyper-glycemias / potassium ion-transporting ATPase complex / positive regulation of tight junction disassembly / negative regulation of low-density lipoprotein particle clearance / negative regulation of blood-brain barrier permeability / ATP-activated inward rectifier potassium channel activity / glutamate secretion, neurotransmission / inward rectifying potassium channel / sulfonylurea receptor activity / positive regulation of potassium ion transport / ATPase-coupled monoatomic cation transmembrane transporter activity / response to pH / inorganic cation transmembrane transport / neuromuscular process / negative regulation of glial cell proliferation / response to zinc ion / potassium ion import across plasma membrane / intracellular glucose homeostasis / positive regulation of insulin secretion involved in cellular response to glucose stimulus / ATPase-coupled transmembrane transporter activity / potassium channel activity / ABC-type transporter activity / negative regulation of insulin secretion / potassium ion transmembrane transport / negative regulation of angiogenesis / Regulation of insulin secretion / female pregnancy / ADP binding / response to insulin / visual learning / potassium ion transport / transmembrane transport / sarcolemma / memory / synaptic vesicle membrane / positive regulation of tumor necrosis factor production / transmembrane transporter binding / response to lipopolysaccharide / response to xenobiotic stimulus / ATP hydrolysis activity / ATP binding / membrane / plasma membrane
Similarity search - Function
ATP-binding cassette subfamily C member 8 / Sulphonylurea receptor / : / ABC transporter transmembrane region / ABC transporter type 1, transmembrane domain / ABC transporter integral membrane type-1 fused domain profile. / ABC transporter type 1, transmembrane domain superfamily / ABC transporter-like, conserved site / ABC transporters family signature. / ABC transporter ...ATP-binding cassette subfamily C member 8 / Sulphonylurea receptor / : / ABC transporter transmembrane region / ABC transporter type 1, transmembrane domain / ABC transporter integral membrane type-1 fused domain profile. / ABC transporter type 1, transmembrane domain superfamily / ABC transporter-like, conserved site / ABC transporters family signature. / ABC transporter / ABC transporter-like, ATP-binding domain / ATP-binding cassette, ABC transporter-type domain profile. / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
ADENOSINE-5'-DIPHOSPHATE / ADENOSINE-5'-TRIPHOSPHATE / ATP-binding cassette sub-family C member 8
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsZhao, C. / MacKinnon, R.
Funding support United States, 1items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: Proc Natl Acad Sci U S A / Year: 2021
Title: Molecular structure of an open human K channel.
Authors: Chen Zhao / Roderick MacKinnon /
Abstract: K channels are metabolic sensors that translate intracellular ATP/ADP balance into membrane excitability. The molecular composition of K includes an inward-rectifier potassium channel (Kir) and an ...K channels are metabolic sensors that translate intracellular ATP/ADP balance into membrane excitability. The molecular composition of K includes an inward-rectifier potassium channel (Kir) and an ABC transporter-like sulfonylurea receptor (SUR). Although structures of K have been determined in many conformations, in all cases, the pore in Kir is closed. Here, we describe human pancreatic K (hK) structures with an open pore at 3.1- to 4.0-Å resolution using single-particle cryo-electron microscopy (cryo-EM). Pore opening is associated with coordinated structural changes within the ATP-binding site and the channel gate in Kir. Conformational changes in SUR are also observed, resulting in an area reduction of contact surfaces between SUR and Kir. We also observe that pancreatic hK exhibits the unique (among inward-rectifier channels) property of PIP-independent opening, which appears to be correlated with a docked cytoplasmic domain in the absence of PIP.
History
DepositionSep 12, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 1, 2021Provider: repository / Type: Initial release
Revision 1.1Dec 8, 2021Group: Database references / Category: citation / Item: _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Jun 5, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond

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Structure visualization

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Assembly

Deposited unit
E: ATP-binding cassette sub-family C member 8
hetero molecules


Theoretical massNumber of molelcules
Total (without water)178,0895
Polymers177,1061
Non-polymers9834
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein ATP-binding cassette sub-family C member 8 / Sulfonylurea receptor 1


Mass: 177106.078 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ABCC8, HRINS, SUR, SUR1 / Production host: Homo sapiens (human) / References: UniProt: Q09428
#2: Chemical ChemComp-ADP / ADENOSINE-5'-DIPHOSPHATE


Mass: 427.201 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H15N5O10P2 / Feature type: SUBJECT OF INVESTIGATION / Comment: ADP, energy-carrying molecule*YM
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-ATP / ADENOSINE-5'-TRIPHOSPHATE


Mass: 507.181 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H16N5O13P3 / Feature type: SUBJECT OF INVESTIGATION / Comment: ATP, energy-carrying molecule*YM
Has ligand of interestY

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Experimental details

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Experiment

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

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Sample preparation

ComponentName: Human KATP channel composed of Kir6.2 (C166S G334D) and SUR1
Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Molecular weightValue: 881.87 kDa/nm / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 8.5
SpecimenConc.: 6.83 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 289 K

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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 FIELD / C2 aperture diameter: 100 µm
Image recordingElectron dose: 57 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

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Processing

SoftwareName: PHENIX / Version: 1.17.1_3660: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 144706 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00611195
ELECTRON MICROSCOPYf_angle_d0.81115218
ELECTRON MICROSCOPYf_dihedral_angle_d18.0771517
ELECTRON MICROSCOPYf_chiral_restr0.0521813
ELECTRON MICROSCOPYf_plane_restr0.0071872

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