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- EMDB-41036: Closed human HCN1 F186C S264C bound to cAMP, reconstituted in LMN... -
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Open data
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Basic information
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Title | Closed human HCN1 F186C S264C bound to cAMP, reconstituted in LMNG + SPL | |||||||||
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![]() | Ion Channel / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() intracellular cAMP-activated cation channel activity involved in regulation of presynaptic membrane potential / HCN channels / general adaptation syndrome, behavioral process / HCN channel complex / retinal cone cell development / regulation of membrane depolarization / intracellularly cAMP-activated cation channel activity / apical protein localization / voltage-gated monoatomic cation channel activity / voltage-gated sodium channel activity ...intracellular cAMP-activated cation channel activity involved in regulation of presynaptic membrane potential / HCN channels / general adaptation syndrome, behavioral process / HCN channel complex / retinal cone cell development / regulation of membrane depolarization / intracellularly cAMP-activated cation channel activity / apical protein localization / voltage-gated monoatomic cation channel activity / voltage-gated sodium channel activity / voltage-gated potassium channel activity / potassium channel activity / neuronal action potential / sodium ion transmembrane transport / cAMP binding / cellular response to cAMP / presynaptic active zone membrane / potassium ion transmembrane transport / regulation of membrane potential / postsynaptic membrane / protein homotetramerization / axon / glutamatergic synapse / dendrite / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.16 Å | |||||||||
![]() | Burtscher V / Mount J / Cowgill J / Chang Y / Bickel K / Yuan P / Chanda B | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for hyperpolarization-dependent opening of human HCN1 channel. Authors: Verena Burtscher / Jonathan Mount / Jian Huang / John Cowgill / Yongchang Chang / Kathleen Bickel / Jianhan Chen / Peng Yuan / Baron Chanda / ![]() ![]() Abstract: Hyperpolarization and cyclic nucleotide (HCN) activated ion channels are critical for the automaticity of action potentials in pacemaking and rhythmic electrical circuits in the human body. Unlike ...Hyperpolarization and cyclic nucleotide (HCN) activated ion channels are critical for the automaticity of action potentials in pacemaking and rhythmic electrical circuits in the human body. Unlike most voltage-gated ion channels, the HCN and related plant ion channels activate upon membrane hyperpolarization. Although functional studies have identified residues in the interface between the voltage-sensing and pore domain as crucial for inverted electromechanical coupling, the structural mechanisms for this unusual voltage-dependence remain unclear. Here, we present cryo-electron microscopy structures of human HCN1 corresponding to Closed, Open, and a putative Intermediate state. Our structures reveal that the downward motion of the gating charges past the charge transfer center is accompanied by concomitant unwinding of the inner end of the S4 and S5 helices, disrupting the tight gating interface observed in the Closed state structure. This helix-coil transition at the intracellular gating interface accompanies a concerted iris-like dilation of the pore helices and underlies the reversed voltage dependence of HCN channels. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 86.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.1 KB 19.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.2 KB | Display | ![]() |
Images | ![]() | 143.6 KB | ||
Filedesc metadata | ![]() | 6.6 KB | ||
Others | ![]() ![]() | 95.4 MB 95.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8t4mMC ![]() 8t4yC ![]() 8t50C C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.928 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_41036_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_41036_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Tetrameric hHCN1
Entire | Name: Tetrameric hHCN1 |
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Components |
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-Supramolecule #1: Tetrameric hHCN1
Supramolecule | Name: Tetrameric hHCN1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 / Details: Homotetramer |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Potassium/sodium hyperpolarization-activated cyclic nucleotide-ga...
Macromolecule | Name: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 98.87182 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: 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 NVASDTVCLL DLIMNFRTGT VNEDSSEIIL DPKVIKMNYL KSWFVVDFIS SIPVDYIFLI VE KGMDSEV YKTARALRIV RFTKILCLLR LLRLSRLIRY IHQWEEIFHM TYDLASAVVR IFNLIGMMLL LCHWDGCLQF LVP LLQDFP PDCWVSLNEM VNDSWGKQYS YALFKAMSHM LCIGYGAQAP VSMSDLWITM LSMIVGATCY AMFVGHATAL IQSL DSSRR QYQEKYKQVE QYMSFHKLPA DMRQKIHDYY EHRYQGKIFD EENILNELND PLREEIVNFN CRKLVATMPL FANAD PNFV TAMLSKLRFE VFQPGDYIIR EGAVGKKMYF IQHGVAGVIT KSSKEMKLTD GSYFGEICLL TKGRRTASVR ADTYCR LYS LSVDNFNEVL EEYPMMRRAF ETVAIDRLDR IGKKNSILLQ KFQKDLNTGV FNNQENEILK QIVKHDREMV QAIAPIN YP QMTTLNSTSS TTTPTSRMRT QSPPVYTATS LSHSNLHSPS PSTQTPQPSA ILSPCSYTTA VCSPPVQSPL AARTFHYA S PTASQLSLMQ QQPQQQVQQS QPPQTQPQQP SPQPQTPGSS TPKNEVHKST QALHNTNLTR EVRPLSASQP SLPHEVSTL ISRPHPTVGE SLASIPQPVT AVPGTGLQAG GRSTVPQRVT LFRQMSSGAI PPNRGVPPAP PPPAAALPRE SSSVLNTDPD AEKPRFASN L UniProtKB: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 |
-Macromolecule #2: ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE
Macromolecule | Name: ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE / type: ligand / ID: 2 / Number of copies: 4 / Formula: CMP |
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Molecular weight | Theoretical: 329.206 Da |
Chemical component information | ![]() ChemComp-CMP: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 2.5 mg/mL | |||||||||||||||||||||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil / Material: COPPER / Mesh: 200 | |||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 4 K / Instrument: FEI VITROBOT MARK III |
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Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 1973 / Average exposure time: 9.77 sec. / Average electron dose: 53.07 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.4 mm / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.8 µm |