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- EMDB-26581: Human Kv4.2-KChIP2-DPP6 channel complex in an open state, intrace... -

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Basic information

Entry
Database: EMDB / ID: EMD-26581
TitleHuman Kv4.2-KChIP2-DPP6 channel complex in an open state, intracellular region
Map data
Sample
  • Complex: Human Kv4.2-KChIP2-DPP6 channel complex in an open state, intracellular region
    • Protein or peptide: Potassium voltage-gated channel subfamily D member 2
    • Protein or peptide: Isoform 2 of Kv channel-interacting protein 2
  • Ligand: ZINC ION
  • Ligand: CALCIUM ION
Keywordspotassium channel complex / MEMBRANE PROTEIN
Function / homology
Function and homology information


ER retention sequence binding / positive regulation of voltage-gated potassium channel activity / Kv4.2-KChIP2 channel complex / clustering of voltage-gated potassium channels / A-type (transient outward) potassium channel activity / Phase 1 - inactivation of fast Na+ channels / positive regulation of potassium ion export across plasma membrane / voltage-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / potassium channel complex / membrane repolarization during cardiac muscle cell action potential ...ER retention sequence binding / positive regulation of voltage-gated potassium channel activity / Kv4.2-KChIP2 channel complex / clustering of voltage-gated potassium channels / A-type (transient outward) potassium channel activity / Phase 1 - inactivation of fast Na+ channels / positive regulation of potassium ion export across plasma membrane / voltage-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / potassium channel complex / membrane repolarization during cardiac muscle cell action potential / potassium ion export across plasma membrane / membrane repolarization / Voltage gated Potassium channels / regulation of potassium ion transmembrane transport / postsynaptic specialization membrane / anchoring junction / action potential / regulation of heart contraction / neuronal cell body membrane / voltage-gated potassium channel activity / potassium channel activity / plasma membrane raft / locomotor rhythm / detection of calcium ion / GABA-ergic synapse / potassium channel regulator activity / neuronal action potential / potassium ion transmembrane transport / voltage-gated potassium channel complex / sensory perception of pain / muscle contraction / potassium ion transport / protein homooligomerization / cellular response to hypoxia / chemical synaptic transmission / postsynaptic membrane / perikaryon / transmembrane transporter binding / dendritic spine / neuronal cell body / glutamatergic synapse / synapse / calcium ion binding / dendrite / protein-containing complex binding / signal transduction / identical protein binding / metal ion binding / plasma membrane / cytoplasm
Similarity search - Function
Potassium channel, voltage dependent, Kv4.2 / Potassium channel, voltage dependent, Kv4 / Shal-type voltage-gated potassium channels, N-terminal / Potassium channel, voltage dependent, Kv4, C-terminal / Shal-type voltage-gated potassium channels, N-terminal / Domain of unknown function (DUF3399) / Recoverin family / Potassium channel, voltage dependent, Kv / Potassium channel tetramerisation-type BTB domain / BTB/POZ domain ...Potassium channel, voltage dependent, Kv4.2 / Potassium channel, voltage dependent, Kv4 / Shal-type voltage-gated potassium channels, N-terminal / Potassium channel, voltage dependent, Kv4, C-terminal / Shal-type voltage-gated potassium channels, N-terminal / Domain of unknown function (DUF3399) / Recoverin family / Potassium channel, voltage dependent, Kv / Potassium channel tetramerisation-type BTB domain / BTB/POZ domain / EF-hand domain pair / Broad-Complex, Tramtrack and Bric a brac / BTB/POZ domain / Voltage-dependent channel domain superfamily / SKP1/BTB/POZ domain superfamily / EF-hand domain pair / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site / EF-hand calcium-binding domain. / EF-hand calcium-binding domain profile. / EF-hand domain / Ion transport domain / Ion transport protein / EF-hand domain pair
Similarity search - Domain/homology
Kv channel-interacting protein 2 / Potassium voltage-gated channel subfamily D member 2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.33 Å
AuthorsZhao H / Dai Y / Lee CH
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM143282 United States
CitationJournal: Mol Cell / Year: 2022
Title: Activation and closed-state inactivation mechanisms of the human voltage-gated K4 channel complexes.
Authors: Wenlei Ye / Hongtu Zhao / Yaxin Dai / Yingdi Wang / Yu-Hua Lo / Lily Yeh Jan / Chia-Hsueh Lee /
Abstract: The voltage-gated ion channel activity depends on both activation (transition from the resting state to the open state) and inactivation. Inactivation is a self-restraint mechanism to limit ion ...The voltage-gated ion channel activity depends on both activation (transition from the resting state to the open state) and inactivation. Inactivation is a self-restraint mechanism to limit ion conduction and is as crucial to membrane excitability as activation. Inactivation can occur when the channel is open or closed. Although open-state inactivation is well understood, the molecular basis of closed-state inactivation has remained elusive. We report cryo-EM structures of human K4.2 channel complexes in inactivated, open, and closed states. Closed-state inactivation of K4 involves an unprecedented symmetry breakdown for pore closure by only two of the four S4-S5 linkers, distinct from known mechanisms of open-state inactivation. We further capture K4 in a putative resting state, revealing how voltage sensor movements control the pore. Moreover, our structures provide insights regarding channel modulation by KChIP2 and DPP6 auxiliary subunits. Our findings elucidate mechanisms of closed-state inactivation and voltage-dependent activation of the K4 channel.
History
DepositionApr 1, 2022-
Header (metadata) releaseJun 29, 2022-
Map releaseJun 29, 2022-
UpdateFeb 14, 2024-
Current statusFeb 14, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_26581.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.826 Å
Density
Contour LevelBy AUTHOR: 0.6
Minimum - Maximum-2.695609 - 4.2937436
Average (Standard dev.)-0.0027634357 (±0.07080577)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions480480480
Spacing480480480
CellA=B=C: 396.47998 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_26581_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_26581_half_map_2.map
Projections & Slices
AxesZYX

Projections

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Sample components

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Entire : Human Kv4.2-KChIP2-DPP6 channel complex in an open state, intrace...

EntireName: Human Kv4.2-KChIP2-DPP6 channel complex in an open state, intracellular region
Components
  • Complex: Human Kv4.2-KChIP2-DPP6 channel complex in an open state, intracellular region
    • Protein or peptide: Potassium voltage-gated channel subfamily D member 2
    • Protein or peptide: Isoform 2 of Kv channel-interacting protein 2
  • Ligand: ZINC ION
  • Ligand: CALCIUM ION

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Supramolecule #1: Human Kv4.2-KChIP2-DPP6 channel complex in an open state, intrace...

SupramoleculeName: Human Kv4.2-KChIP2-DPP6 channel complex in an open state, intracellular region
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Potassium voltage-gated channel subfamily D member 2

MacromoleculeName: Potassium voltage-gated channel subfamily D member 2 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 59.049332 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MAAGVAAWLP FARAAAIGWM PVASGPMPAP PRQERKRTQD ALIVLNVSGT RFQTWQDTLE RYPDTLLGSS ERDFFYHPET QQYFFDRDP DIFRHILNFY RTGKLHYPRH ECISAYDEEL AFFGLIPEII GDCCYEEYKD RRRENAERLQ DDADTDTAGE S ALPTMTAR ...String:
MAAGVAAWLP FARAAAIGWM PVASGPMPAP PRQERKRTQD ALIVLNVSGT RFQTWQDTLE RYPDTLLGSS ERDFFYHPET QQYFFDRDP DIFRHILNFY RTGKLHYPRH ECISAYDEEL AFFGLIPEII GDCCYEEYKD RRRENAERLQ DDADTDTAGE S ALPTMTAR QRVWRAFENP HTSTMALVFY YVTGFFIAVS VIANVVETVP CGSSPGHIKE LPCGERYAVA FFCLDTACVM IF TVEYLLR LAAAPSRYRF VRSVMSIIDV VAILPYYIGL VMTDNEDVSG AFVTLRVFRV FRIFKFSRHS QGLRILGYTL KSC ASELGF LLFSLTMAII IFATVMFYAE KGSSASKFTS IPAAFWYTIV TMTTLGYGDM VPKTIAGKIF GSICSLSGVL VIAL PVPVI VSNFSRIYHQ NQRADKRRAQ KKARLARIRA AKSGSANAYM QSKRNGLLSN QLQSSEDEQA FVSKSGSSFE TQHHH LLHC LEKTTNHEFV DEQVFEESCM EVATVNRPSS HSPSLSSQQG

UniProtKB: Potassium voltage-gated channel subfamily D member 2

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Macromolecule #2: Isoform 2 of Kv channel-interacting protein 2

MacromoleculeName: Isoform 2 of Kv channel-interacting protein 2 / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 28.975486 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MRGQGRKESL SDSRDLDGSY DQLTGHPPGP TKKALKQRFL KLLPCCGPQA LPSVSENSVD DEFELSTVCH RPEGLEQLQE QTKFTRKEL QVLYRGFKNE CPSGIVNEEN FKQIYSQFFP QGDSSTYATF LFNAFDTNHD GSVSFEDFVA GLSVILRGTV D DRLNWAFN ...String:
MRGQGRKESL SDSRDLDGSY DQLTGHPPGP TKKALKQRFL KLLPCCGPQA LPSVSENSVD DEFELSTVCH RPEGLEQLQE QTKFTRKEL QVLYRGFKNE CPSGIVNEEN FKQIYSQFFP QGDSSTYATF LFNAFDTNHD GSVSFEDFVA GLSVILRGTV D DRLNWAFN LYDLNKDGCI TKEEMLDIMK SIYDMMGKYT YPALREEAPR EHVESFFQKM DRNKDGVVTI EEFIESCQKD EN IMRSMQL FDNVI

UniProtKB: Kv channel-interacting protein 2

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Macromolecule #3: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 3 / Number of copies: 4 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

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Macromolecule #4: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 4 / Number of copies: 12 / Formula: CA
Molecular weightTheoretical: 40.078 Da

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 85.9 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.6 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.33 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 278343
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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