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- EMDB-65357: channel A complex with 1 -

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Basic information

Entry
Database: EMDB / ID: EMD-65357
Titlechannel A complex with 1
Map data
Sample
  • Complex: channel A in complex 1
    • Protein or peptide: Calmodulin-1
    • Protein or peptide: Small conductance calcium-activated potassium channel protein 2
    • Protein or peptide: Apamin
  • Ligand: POTASSIUM ION
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
Keywordschannel A complex with 1 / MEMBRANE PROTEIN
Function / homology
Function and homology information


negative regulation of inward rectifier potassium channel activity / inward rectifier potassium channel inhibitor activity / venom-mediated perturbation of biological process / small conductance calcium-activated potassium channel activity / Acetylcholine inhibits contraction of outer hair cells / negative regulation of potassium ion transmembrane transporter activity / membrane repolarization during atrial cardiac muscle cell action potential / negative regulation of potassium ion transmembrane transport / Ca2+ activated K+ channels / calcium-activated potassium channel activity ...negative regulation of inward rectifier potassium channel activity / inward rectifier potassium channel inhibitor activity / venom-mediated perturbation of biological process / small conductance calcium-activated potassium channel activity / Acetylcholine inhibits contraction of outer hair cells / negative regulation of potassium ion transmembrane transporter activity / membrane repolarization during atrial cardiac muscle cell action potential / negative regulation of potassium ion transmembrane transport / Ca2+ activated K+ channels / calcium-activated potassium channel activity / potassium channel inhibitor activity / inward rectifier potassium channel activity / regulation of potassium ion transmembrane transport / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / Calmodulin induced events / Reduction of cytosolic Ca++ levels / Activation of Ca-permeable Kainate Receptor / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Loss of phosphorylation of MECP2 at T308 / CREB1 phosphorylation through the activation of Adenylate Cyclase / negative regulation of high voltage-gated calcium channel activity / PKA activation / CaMK IV-mediated phosphorylation of CREB / Glycogen breakdown (glycogenolysis) / CLEC7A (Dectin-1) induces NFAT activation / Activation of RAC1 downstream of NMDARs / negative regulation of ryanodine-sensitive calcium-release channel activity / organelle localization by membrane tethering / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / negative regulation of calcium ion export across plasma membrane / regulation of cardiac muscle cell action potential / presynaptic endocytosis / Synthesis of IP3 and IP4 in the cytosol / regulation of cell communication by electrical coupling involved in cardiac conduction / Phase 0 - rapid depolarisation / alpha-actinin binding / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / calcineurin-mediated signaling / RHO GTPases activate PAKs / regulation of ryanodine-sensitive calcium-release channel activity / Ion transport by P-type ATPases / Uptake and function of anthrax toxins / Long-term potentiation / protein phosphatase activator activity / Calcineurin activates NFAT / Regulation of MECP2 expression and activity / DARPP-32 events / Smooth Muscle Contraction / detection of calcium ion / regulation of cardiac muscle contraction / catalytic complex / RHO GTPases activate IQGAPs / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / calcium channel inhibitor activity / presynaptic cytosol / Activation of AMPK downstream of NMDARs / cellular response to interferon-beta / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / Protein methylation / Ion homeostasis / eNOS activation / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / titin binding / regulation of calcium-mediated signaling / voltage-gated potassium channel complex / potassium ion transmembrane transport / FCERI mediated Ca+2 mobilization / calcium channel complex / substantia nigra development / regulation of heart rate / FCGR3A-mediated IL10 synthesis / Ras activation upon Ca2+ influx through NMDA receptor / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / calyx of Held / adenylate cyclase activator activity / VEGFR2 mediated cell proliferation / sarcomere / protein serine/threonine kinase activator activity / regulation of cytokinesis / VEGFR2 mediated vascular permeability / spindle microtubule / positive regulation of receptor signaling pathway via JAK-STAT / Translocation of SLC2A4 (GLUT4) to the plasma membrane / calcium channel regulator activity / potassium ion transport / RAF activation / Transcriptional activation of mitochondrial biogenesis / response to calcium ion / cellular response to type II interferon / G2/M transition of mitotic cell cycle / Stimuli-sensing channels / Z disc / spindle pole / Signaling by RAF1 mutants / RAS processing / Signaling by moderate kinase activity BRAF mutants
Similarity search - Function
Honey bee toxin / Honey bee toxin / Calmodulin-binding domain / Potassium channel, calcium-activated, SK / SK, calmodulin-binding domain superfamily / Calmodulin binding domain / Calcium-activated SK potassium channel / Calmodulin binding domain / Potassium channel domain / Ion channel ...Honey bee toxin / Honey bee toxin / Calmodulin-binding domain / Potassium channel, calcium-activated, SK / SK, calmodulin-binding domain superfamily / Calmodulin binding domain / Calcium-activated SK potassium channel / Calmodulin binding domain / Potassium channel domain / Ion channel / : / 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 / EF-hand domain pair
Similarity search - Domain/homology
Apamin / Calmodulin-1 / Small conductance calcium-activated potassium channel protein 2
Similarity search - Component
Biological speciesHomo sapiens (human) / Apis mellifera (honey bee)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.23 Å
AuthorsJiang DH / Ma B
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)31971134 China
CitationJournal: Nat Commun / Year: 2026
Title: Structural mechanisms for inhibition and activation of human small-conductance Ca-activated potassium channel SK2.
Authors: Bao Ma / Di Wu / En Cao / Cheng Chi / Zhihao Wang / Zhanyi Xia / Long-Hua Sun / Bingxing Pan / Daohua Jiang / Wenhua Zhang /
Abstract: The small-conductance calcium-activated potassium (SK1-3 or K2) channels regulate the intrinsic excitability and firing frequency of excitable cells. SK channels are modulated by a variety of ...The small-conductance calcium-activated potassium (SK1-3 or K2) channels regulate the intrinsic excitability and firing frequency of excitable cells. SK channels are modulated by a variety of distinct modulators; however, the underlying mechanisms remain elusive. Here, we present four cryoelectron microscopy structures of the human SK2-calmodulin complex bound with apamin, UCL1684, AP30663, and CAD-1883, elucidating their distinct binding sites and regulatory mechanisms. Apamin and UCL1684 compete for a similar binding site above the selectivity filter, which is formed by the distinct S3-S4 linker of SK2. CAD-1883 glues the N-lobe of calmodulin and the S4-S5 linker of SK2, reinforcing the open state. In contrast, AP30663 resides in the central cavity of SK2, blocking ion conductance. This study reveals multiple modulation sites in SK2 and the molecular mechanisms for the inhibition and potentiation of SK channels, which could advance rational drug design targeting SK2 channel for the treatment of cardiovascular and neurological disorders.
History
DepositionJul 12, 2025-
Header (metadata) releaseMar 11, 2026-
Map releaseMar 11, 2026-
UpdateMar 11, 2026-
Current statusMar 11, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_65357.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 320 pix.
= 272. Å
0.85 Å/pix.
x 320 pix.
= 272. Å
0.85 Å/pix.
x 320 pix.
= 272. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.85 Å
Density
Contour LevelBy AUTHOR: 0.144
Minimum - Maximum-0.7575549 - 1.1614232
Average (Standard dev.)-0.00036763874 (±0.025486188)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 272.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_65357_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_65357_half_map_2.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

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Sample components

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Entire : channel A in complex 1

EntireName: channel A in complex 1
Components
  • Complex: channel A in complex 1
    • Protein or peptide: Calmodulin-1
    • Protein or peptide: Small conductance calcium-activated potassium channel protein 2
    • Protein or peptide: Apamin
  • Ligand: POTASSIUM ION
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate

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Supramolecule #1: channel A in complex 1

SupramoleculeName: channel A in complex 1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Calmodulin-1

MacromoleculeName: Calmodulin-1 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 16.852545 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MADQLTEEQI AEFKEAFSLF DKDGDGTITT KELGTVMRSL GQNPTEAELQ DMINEVDADG NGTIDFPEFL TMMARKMKDT DSEEEIREA FRVFDKDGNG YISAAELRHV MTNLGEKLTD EEVDEMIREA DIDGDGQVNY EEFVQMMTAK

UniProtKB: Calmodulin-1

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Macromolecule #2: Small conductance calcium-activated potassium channel protein 2

MacromoleculeName: Small conductance calcium-activated potassium channel protein 2
type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 63.841598 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MSSCRYNGGV MRPLSNLSAS RRNLHEMDSE AQPLQPPASV GGGGGASSPS AAAAAAAAVS SSAPEIVVSK PEHNNSNNLA LYGTGGGGS TGGGGGGGGS GHGSSSGTKS SKKKNQNIGY KLGHRRALFE KRKRLSDYAL IFGMFGIVVM VIETELSWGA Y DKASLYSL ...String:
MSSCRYNGGV MRPLSNLSAS RRNLHEMDSE AQPLQPPASV GGGGGASSPS AAAAAAAAVS SSAPEIVVSK PEHNNSNNLA LYGTGGGGS TGGGGGGGGS GHGSSSGTKS SKKKNQNIGY KLGHRRALFE KRKRLSDYAL IFGMFGIVVM VIETELSWGA Y DKASLYSL ALKCLISLST IILLGLIIVY HAREIQLFMV DNGADDWRIA MTYERIFFIC LEILVCAIHP IPGNYTFTWT AR LAFSYAP STTTADVDII LSIPMFLRLY LIARVMLLHS KLFTDASSRS IGALNKINFN TRFVMKTLMT ICPGTVLLVF SIS LWIIAA WTVRACERYH DQQDVTSNFL GAMWLISITF LSIGYGDMVP NTYCGKGVCL LTGIMGAGCT ALVVAVVARK LELT KAEKH VHNFMMDTQL TKRVKNAAAN VLRETWLIYK NTKLVKKIDH AKVRKHQRKF LQAIHQLRSV KMEQRKLNDQ ANTLV DLAK TQNIMYDMIS DLNERSEDFE KRIVTLETKL ETLIGSIHAL PGLISQTIRQ QQRDFIEAQM ESYDKHVTYN AERSRS SSR RRRSSSTAPP TSSESS

UniProtKB: Small conductance calcium-activated potassium channel protein 2

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Macromolecule #3: Apamin

MacromoleculeName: Apamin / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Apis mellifera (honey bee)
Molecular weightTheoretical: 2.036385 KDa
Recombinant expressionOrganism: Apis mellifera (honey bee)
SequenceString:
CNCKAPETAL CARRCQQH

UniProtKB: Apamin

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Macromolecule #4: POTASSIUM ION

MacromoleculeName: POTASSIUM ION / type: ligand / ID: 4 / Number of copies: 4 / Formula: K
Molecular weightTheoretical: 39.098 Da

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Macromolecule #5: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...

MacromoleculeName: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
type: ligand / ID: 5 / Number of copies: 4 / Formula: POV
Molecular weightTheoretical: 760.076 Da
Chemical component information

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM

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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: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.23 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 67421
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD

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