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- EMDB-53516: Structure of the human chimera HCN112 hyperpolarization-activated... -

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Basic information

Entry
Database: EMDB / ID: EMD-53516
TitleStructure of the human chimera HCN112 hyperpolarization-activated cyclic nucleotide-gated ion channel.
Map data
Sample
  • Complex: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
    • Protein or peptide: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1,Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2
KeywordsIon channel / HCN channel / pacemaker channel / MEMBRANE PROTEIN
Function / homology
Function and homology information


: / positive regulation of membrane hyperpolarization / HCN channels / general adaptation syndrome, behavioral process / cellular response to aldosterone / HCN channel complex / retinal cone cell development / ammonium transmembrane transport / cellular response to cGMP / intracellularly cAMP-activated cation channel activity ...: / positive regulation of membrane hyperpolarization / HCN channels / general adaptation syndrome, behavioral process / cellular response to aldosterone / HCN channel complex / retinal cone cell development / ammonium transmembrane transport / cellular response to cGMP / intracellularly cAMP-activated cation channel activity / negative regulation of action potential / regulation of SA node cell action potential / membrane depolarization during cardiac muscle cell action potential / maternal behavior / apical dendrite / sodium ion import across plasma membrane / apical protein localization / response to L-glutamate / negative regulation of synaptic transmission, glutamatergic / voltage-gated sodium channel activity / voltage-gated monoatomic cation channel activity / regulation of membrane depolarization / potassium ion import across plasma membrane / phosphatidylinositol-3,4,5-trisphosphate binding / regulation of heart rate by cardiac conduction / voltage-gated potassium channel activity / potassium channel activity / cAMP binding / neuronal action potential / cellular response to interferon-beta / phosphatidylinositol-4,5-bisphosphate binding / voltage-gated potassium channel complex / presynaptic active zone membrane / potassium ion transmembrane transport / dendrite membrane / axon terminus / cellular response to cAMP / dendritic shaft / sodium ion transmembrane transport / PDZ domain binding / regulation of membrane potential / response to calcium ion / cell-cell signaling / protein homotetramerization / molecular adaptor activity / basolateral plasma membrane / postsynaptic membrane / response to xenobiotic stimulus / axon / neuronal cell body / dendrite / protein-containing complex binding / glutamatergic synapse / cell surface / identical protein binding / plasma membrane
Similarity search - Function
Ion transport N-terminal / Ion transport protein N-terminal / : / Potassium channel, voltage-dependent, EAG/ELK/ERG / Cyclic nucleotide-binding domain signature 1. / Cyclic nucleotide-binding, conserved site / Cyclic nucleotide-monophosphate binding domain / Cyclic nucleotide-binding domain / cAMP/cGMP binding motif profile. / Cyclic nucleotide-binding domain ...Ion transport N-terminal / Ion transport protein N-terminal / : / Potassium channel, voltage-dependent, EAG/ELK/ERG / Cyclic nucleotide-binding domain signature 1. / Cyclic nucleotide-binding, conserved site / Cyclic nucleotide-monophosphate binding domain / Cyclic nucleotide-binding domain / cAMP/cGMP binding motif profile. / Cyclic nucleotide-binding domain / Cyclic nucleotide-binding domain superfamily / RmlC-like jelly roll fold / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 / Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.53 Å
AuthorsZorzini V / Ulens C
Funding support Belgium, 2 items
OrganizationGrant numberCountry
Research Foundation - Flanders (FWO)12W4618N Belgium
Research Foundation - Flanders (FWO) Belgium
CitationJournal: To Be Published
Title: Interactions between CNBD and HCND domains control gating inhibition in HCN1 family.
Authors: Zorzini V / Gallardo R / Brams M / Ulens C
History
DepositionApr 28, 2025-
Header (metadata) releaseMay 13, 2026-
Map releaseMay 13, 2026-
UpdateMay 13, 2026-
Current statusMay 13, 2026Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_53516.png

Downloads & links

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Map

FileDownload / File: emd_53516.map.gz / Format: CCP4 / Size: 163.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.81 Å/pix.
x 350 pix.
= 283.5 Å		0.81 Å/pix.
x 350 pix.
= 283.5 Å		0.81 Å/pix.
x 350 pix.
= 283.5 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.81 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.35
Minimum - Maximum-1.750738 - 3.0518131
Average (Standard dev.)0.0034599213 (±0.06528395)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions350350350
Spacing350350350
CellA=B=C: 283.5 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_53516_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_53516_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Potassium/sodium hyperpolarization-activated cyclic nucleotide-ga...

EntireName: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Components
  • Complex: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
    • Protein or peptide: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1,Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2

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Supramolecule #1: Potassium/sodium hyperpolarization-activated cyclic nucleotide-ga...

SupramoleculeName: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all / Details: HCN112 Chimera between HCN1 and HCN2
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Potassium/sodium hyperpolarization-activated cyclic nucleotide-ga...

MacromoleculeName: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1,Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2
type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 74.099016 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MEGGGKPNSS SNSRDDGNSV FPAKASATGA GPAAAEKRLG TPPGGGGAGA KEHGNSVCFK VDGGGGGGGG GGGGEEPAGG FEDAEGPRR QYGFMQRQFT SMLQPGVNKF SLRMFGSQKA VEKEQERVKT AGFWIIHPYS DFRFYWDLIM LIMMVGNLVI I PVGITFFT ...String:
MEGGGKPNSS SNSRDDGNSV FPAKASATGA GPAAAEKRLG TPPGGGGAGA KEHGNSVCFK VDGGGGGGGG GGGGEEPAGG FEDAEGPRR QYGFMQRQFT SMLQPGVNKF SLRMFGSQKA VEKEQERVKT AGFWIIHPYS DFRFYWDLIM LIMMVGNLVI I PVGITFFT EQTTTPWIIF NVASDTVFLL DLIMNFRTGT VNEDSSEIIL DPKVIKMNYL KSWFVVDFIS SIPVDYIFLI VE KGMDSEV YKTARALRIV RFTKILSLLR LLRLSRLIRY IHQWEEIFHM TYDLASAVVR IFNLIGMMLL LCHWDGCLQF LVP LLQDFP PDCWVSLNEM VNDSWGKQYS YALFKAMSHM LCIGYGAQAP VSMSDLWITM LSMIVGATCY AMFVGHATAL IQSL DSSRR QYQEKYKQVE QYMSFHKLPA DFRQKIHDYY EHRYQGKMFD EDSILGELNG PLREEIVNFN CRKLVASMPL FANAD PNFV TAMLTKLKFE VFQPGDYIIR EGTIGKKMYF IQHGVVSVLT KGNKEMKLSD GSYFGEICLL TRGRRTASVR ADTYCR LYS LSVDNFNEVL EEYPMMRRAF ETVAIDRLDR IGKKNSILLH KVQHDLNSGV FNNQENAIIQ EIVKYDREMV QQASPGA AG GLDPQDSARS RLSSNL

UniProtKB: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1, Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2

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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

Concentration3.7 mg/mL
BufferpH: 8
GridModel: UltrAuFoil R2/2 / Material: GOLD / Mesh: 200
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 278 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number real images: 5042 / Average exposure time: 6.25 sec. / Average electron dose: 41.42 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.2 µm / Nominal defocus min: 1.6 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 370859
CTF correctionSoftware - Name: RELION (ver. 3.1.2) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Final reconstructionApplied symmetry - Point group: C4 (4 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.53 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 3.2) / Number images used: 92412
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final 3D classificationSoftware - Name: cryoSPARC (ver. 3.2)
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

5u6o


Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL
Output model

PDB-9r1v:
Structure of the human chimera HCN112 hyperpolarization-activated cyclic nucleotide-gated ion channel.

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