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- PDB-8t4y: Human HCN1 F186C S264C C309A bound to cAMP, reconstituted in LMNG... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8t4y | |||||||||
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Title | Human HCN1 F186C S264C C309A bound to cAMP, reconstituted in LMNG + SPL | |||||||||
![]() | Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 | |||||||||
![]() | TRANSPORT PROTEIN / Membrane Protein / Ion Channel | |||||||||
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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.58 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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 351.8 KB | Display | ![]() |
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PDB format | ![]() | 253.7 KB | Display | ![]() |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 41040MC ![]() 8t4mC ![]() 8t50C C: citing same article ( M: map data used to model this data |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 98839.758 Da / Num. of mol.: 4 / Mutation: F186C, S264C, C309A Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Chemical | ChemComp-CMP / Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Human HCN1 Channel / Type: COMPLEX / Details: Homomeric Tetramer / Entity ID: #1 / Source: RECOMBINANT | |||||||||||||||||||||||||||||||||||||||||||||
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Source (natural) | Organism: ![]() | |||||||||||||||||||||||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() | |||||||||||||||||||||||||||||||||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 2.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R2/2 | |||||||||||||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 53.3 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 1 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 167527 | ||||||||||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.58 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 122422 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 8T4M Accession code: 8T4M / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||
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