+Open data
-Basic information
Entry | Database: PDB / ID: 6uqf | |||||||||
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Title | Human HCN1 channel in a hyperpolarized conformation | |||||||||
Components | Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 | |||||||||
Keywords | MEMBRANE PROTEIN / Ion channel | |||||||||
Function / homology | Function and homology information 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 / intracellularly cAMP-activated cation channel activity / apical protein localization / voltage-gated monoatomic cation channel activity / voltage-gated sodium channel activity / regulation of membrane depolarization ...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 / intracellularly cAMP-activated cation channel activity / apical protein localization / voltage-gated monoatomic cation channel activity / voltage-gated sodium channel activity / regulation of membrane depolarization / voltage-gated potassium channel activity / potassium channel activity / neuronal action potential / sodium ion transmembrane transport / presynaptic active zone membrane / cAMP binding / cellular response to cAMP / potassium ion transmembrane transport / regulation of membrane potential / postsynaptic membrane / protein homotetramerization / axon / dendrite / glutamatergic synapse / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.04 Å | |||||||||
Authors | Lee, C.-H. / MacKinnon, R. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Cell / Year: 2019 Title: Voltage Sensor Movements during Hyperpolarization in the HCN Channel. Authors: Chia-Hsueh Lee / Roderick MacKinnon / Abstract: The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is a voltage-gated cation channel that mediates neuronal and cardiac pacemaker activity. The HCN channel exhibits reversed ...The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is a voltage-gated cation channel that mediates neuronal and cardiac pacemaker activity. The HCN channel exhibits reversed voltage dependence, meaning it closes with depolarization and opens with hyperpolarization. Different from Na, Ca, and Kv1-Kv7 channels, the HCN channel does not have domain-swapped voltage sensors. We introduced a reversible, metal-mediated cross bridge into the voltage sensors to create the chemical equivalent of a hyperpolarized conformation and determined the structure using cryoelectron microscopy (cryo-EM). Unlike the depolarized HCN channel, the S4 helix is displaced toward the cytoplasm by two helical turns. Near the cytoplasm, the S4 helix breaks into two helices, one running parallel to the membrane surface, analogous to the S4-S5 linker of domain-swapped voltage-gated channels. These findings suggest a basis for allosteric communication between voltage sensors and the gate in this kind of channel. They also imply that voltage sensor movements are not the same in all voltage-gated channels. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6uqf.cif.gz | 373.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6uqf.ent.gz | 301.2 KB | Display | PDB format |
PDBx/mmJSON format | 6uqf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uq/6uqf ftp://data.pdbj.org/pub/pdb/validation_reports/uq/6uqf | HTTPS FTP |
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-Related structure data
Related structure data | 20846MC 6uqgC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 74615.766 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HCN1, BCNG1 / Production host: Homo sapiens (human) / References: UniProt: O60741 #2: Chemical | ChemComp-CMP / #3: Chemical | ChemComp-HG / Has ligand of interest | N | |
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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 |
-Sample preparation
Component | Name: Human HCN1 channel F186C/S264C / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 75 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.15.2_3472: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.04 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 104860 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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