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- PDB-7uhf: Human L-type voltage-gated calcium channel Cav1.3 in the presence... -

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Basic information

Entry
Database: PDB / ID: 7uhf
TitleHuman L-type voltage-gated calcium channel Cav1.3 in the presence of cinnarizine at 3.1 Angstrom resolution
Components
  • (Voltage-dependent L-type calcium channel subunit ...) x 2
  • Voltage-dependent calcium channel subunit alpha-2/delta-1Voltage-gated calcium channel
KeywordsTRANSPORT PROTEIN / Cav1.3 / Channels / Calcium Ion-Selective
Function / homology
Function and homology information


voltage-gated calcium channel activity involved SA node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / membrane depolarization during SA node cell action potential / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / regulation of potassium ion transmembrane transporter activity / positive regulation of high voltage-gated calcium channel activity / regulation of atrial cardiac muscle cell membrane repolarization / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during bundle of His cell action potential ...voltage-gated calcium channel activity involved SA node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / membrane depolarization during SA node cell action potential / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / regulation of potassium ion transmembrane transporter activity / positive regulation of high voltage-gated calcium channel activity / regulation of atrial cardiac muscle cell membrane repolarization / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during bundle of His cell action potential / positive regulation of adenylate cyclase activity / L-type voltage-gated calcium channel complex / membrane depolarization during cardiac muscle cell action potential / cardiac muscle cell action potential involved in contraction / high voltage-gated calcium channel activity / positive regulation of calcium ion transport / regulation of potassium ion transmembrane transport / NCAM1 interactions / regulation of ventricular cardiac muscle cell membrane repolarization / calcium ion import / Sensory processing of sound by inner hair cells of the cochlea / calcium ion transport into cytosol / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / ankyrin binding / neuromuscular junction development / voltage-gated calcium channel complex / neuronal dense core vesicle / regulation of heart rate by cardiac conduction / alpha-actinin binding / calcium ion import across plasma membrane / calcium channel regulator activity / regulation of calcium ion transport / voltage-gated calcium channel activity / sarcoplasmic reticulum / Regulation of insulin secretion / protein localization to plasma membrane / calcium ion transmembrane transport / sensory perception of sound / calcium channel activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Adrenaline,noradrenaline inhibits insulin secretion / Z disc / cellular response to amyloid-beta / calcium ion transport / T cell receptor signaling pathway / chemical synaptic transmission / synapse / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol
Similarity search - Function
Voltage-dependent calcium channel, L-type, alpha-1D subunit / Voltage-dependent calcium channel, L-type, beta-3 subunit / Voltage-dependent L-type calcium channel subunit beta-3, SH3 domain / Voltage-dependent L-type calcium channel subunit beta-1-4, N-terminal A domain / Voltage-dependent calcium channel, L-type, beta subunit / Voltage gated calcium channel subunit beta domain 4Aa N terminal / Voltage-gated calcium channel subunit alpha, C-terminal / Voltage-gated calcium channel subunit alpha, C-term / Voltage-dependent calcium channel, L-type, alpha-1 subunit / VWA N-terminal ...Voltage-dependent calcium channel, L-type, alpha-1D subunit / Voltage-dependent calcium channel, L-type, beta-3 subunit / Voltage-dependent L-type calcium channel subunit beta-3, SH3 domain / Voltage-dependent L-type calcium channel subunit beta-1-4, N-terminal A domain / Voltage-dependent calcium channel, L-type, beta subunit / Voltage gated calcium channel subunit beta domain 4Aa N terminal / Voltage-gated calcium channel subunit alpha, C-terminal / Voltage-gated calcium channel subunit alpha, C-term / Voltage-dependent calcium channel, L-type, alpha-1 subunit / VWA N-terminal / Voltage-dependent calcium channel, alpha-2/delta subunit, conserved region / VWA N-terminal / Neuronal voltage-dependent calcium channel alpha 2acd / Voltage-dependent calcium channel, alpha-1 subunit, IQ domain / Voltage gated calcium channel IQ domain / Voltage gated calcium channel IQ domain / Voltage-dependent calcium channel, alpha-1 subunit / Voltage-dependent L-type calcium channel, IQ-associated domain / Voltage-dependent L-type calcium channel, IQ-associated / Guanylate kinase/L-type calcium channel beta subunit / Guanylate kinase / Guanylate kinase homologues. / von Willebrand factor type A domain / von Willebrand factor (vWF) type A domain / VWFA domain profile. / Voltage-dependent channel domain superfamily / von Willebrand factor, type A / von Willebrand factor A-like domain superfamily / SH3-like domain superfamily / Ion transport domain / Ion transport protein / Src homology 3 (SH3) domain profile. / SH3 domain / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
1,2-Distearoyl-sn-glycerophosphoethanolamine / Chem-N90 / CHOLESTEROL HEMISUCCINATE / Voltage-dependent L-type calcium channel subunit beta-3 / Voltage-dependent calcium channel subunit alpha-2/delta-1 / Voltage-dependent L-type calcium channel subunit alpha-1D
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsGao, S. / Yao, X. / Yan, N.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM130762 United States
CitationJournal: Cell Res / Year: 2022
Title: Structural basis for pore blockade of human voltage-gated calcium channel Ca1.3 by motion sickness drug cinnarizine.
Authors: Xia Yao / Shuai Gao / Nieng Yan /
History
DepositionMar 26, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 11, 2022Provider: repository / Type: Initial release
Revision 1.1Oct 12, 2022Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Voltage-dependent L-type calcium channel subunit alpha-1D
D: Voltage-dependent calcium channel subunit alpha-2/delta-1
C: Voltage-dependent L-type calcium channel subunit beta-3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)429,79716
Polymers424,7183
Non-polymers5,07913
Water0
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Voltage-dependent L-type calcium channel subunit ... , 2 types, 2 molecules AC

#1: Protein Voltage-dependent L-type calcium channel subunit alpha-1D / Calcium channel / L type / alpha-1 polypeptide / isoform 2 / Voltage-gated calcium channel subunit ...Calcium channel / L type / alpha-1 polypeptide / isoform 2 / Voltage-gated calcium channel subunit alpha Cav1.3


Mass: 245417.734 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CACNA1D, CACH3, CACN4, CACNL1A2, CCHL1A2 / Production host: Homo sapiens (human) / References: UniProt: Q01668
#3: Protein Voltage-dependent L-type calcium channel subunit beta-3 / CAB3 / Calcium channel voltage-dependent subunit beta 3


Mass: 54607.852 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CACNB3, CACNLB3 / Production host: Homo sapiens (human) / References: UniProt: P54284

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Protein , 1 types, 1 molecules D

#2: Protein Voltage-dependent calcium channel subunit alpha-2/delta-1 / Voltage-gated calcium channel / Voltage-gated calcium channel subunit alpha-2/delta-1


Mass: 124692.469 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CACNA2D1, CACNL2A, CCHL2A, MHS3 / Production host: Homo sapiens (human) / References: UniProt: P54289

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Sugars , 4 types, 8 molecules

#4: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 627.594 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,3,2/[a2122h-1b_1-5_2*NCC/3=O]/1-1-1/a4-b1_b4-c1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}}LINUCSPDB-CARE
#5: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#6: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 830.786 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,4,3/[a2122h-1b_1-5_2*NCC/3=O]/1-1-1-1/a4-b1_b4-c1_c4-d1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}}}LINUCSPDB-CARE
#8: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE / N-Acetylglucosamine


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

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Non-polymers , 4 types, 5 molecules

#7: Chemical ChemComp-N90 / 1-(diphenylmethyl)-4-[(2E)-3-phenylprop-2-en-1-yl]piperazine / Cinnarizine / Cinnarizine


Mass: 368.514 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H28N2 / Feature type: SUBJECT OF INVESTIGATION / Comment: chemotherapy, channel blocker*YM
#9: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Ca
#10: Chemical ChemComp-Y01 / CHOLESTEROL HEMISUCCINATE


Mass: 486.726 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C31H50O4
#11: Chemical ChemComp-3PE / 1,2-Distearoyl-sn-glycerophosphoethanolamine / 3-SN-PHOSPHATIDYLETHANOLAMINE / 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE / Phosphatidylethanolamine


Mass: 748.065 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C41H82NO8P / Comment: phospholipid*YM

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Details

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: Cav1.3 / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 281 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 FIELDBright-field microscopy / Nominal defocus max: 2100 nm / Nominal defocus min: 1900 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

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Processing

SoftwareName: PHENIX / Version: 1.19.2_4158: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 51625 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00320818
ELECTRON MICROSCOPYf_angle_d0.56428191
ELECTRON MICROSCOPYf_dihedral_angle_d8.2682850
ELECTRON MICROSCOPYf_chiral_restr0.0443213
ELECTRON MICROSCOPYf_plane_restr0.0043562

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