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Yorodumi- PDB-5u6p: Structure of the human HCN1 hyperpolarization-activated cyclic nu... -
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-Basic information
Entry | Database: PDB / ID: 5u6p | ||||||
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Title | Structure of the human HCN1 hyperpolarization-activated cyclic nucleotide-gated ion channel in complex with cAMP | ||||||
Components | (Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 11) x 2 | ||||||
Keywords | TRANSPORT PROTEIN / pacemaker 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 / 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 / sodium ion transmembrane transport / neuronal action potential / 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 | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.51 Å | ||||||
Authors | Lee, C.-H. / MacKinnon, R. | ||||||
Citation | Journal: Cell / Year: 2017 Title: Structures of the Human HCN1 Hyperpolarization-Activated Channel. Authors: Chia-Hsueh Lee / Roderick MacKinnon / Abstract: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels underlie the control of rhythmic activity in cardiac and neuronal pacemaker cells. In HCN, the polarity of voltage dependence is ...Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels underlie the control of rhythmic activity in cardiac and neuronal pacemaker cells. In HCN, the polarity of voltage dependence is uniquely reversed. Intracellular cyclic adenosine monophosphate (cAMP) levels tune the voltage response, enabling sympathetic nerve stimulation to increase the heart rate. We present cryo-electron microscopy structures of the human HCN channel in the absence and presence of cAMP at 3.5 Å resolution. HCN channels contain a K channel selectivity filter-forming sequence from which the amino acids create a unique structure that explains Na and K permeability. The voltage sensor adopts a depolarized conformation, and the pore is closed. An S4 helix of unprecedented length extends into the cytoplasm, contacts the C-linker, and twists the inner helical gate shut. cAMP binding rotates cytoplasmic domains to favor opening of the inner helical gate. These structures advance understanding of ion selectivity, reversed polarity gating, and cAMP regulation in HCN 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 | 5u6p.cif.gz | 404.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5u6p.ent.gz | 321.9 KB | Display | PDB format |
PDBx/mmJSON format | 5u6p.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5u6p_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 5u6p_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 5u6p_validation.xml.gz | 52.7 KB | Display | |
Data in CIF | 5u6p_validation.cif.gz | 81.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/u6/5u6p ftp://data.pdbj.org/pub/pdb/validation_reports/u6/5u6p | HTTPS FTP |
-Related structure data
Related structure data | 8512MC 8511C 5u6oC 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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Noncrystallographic symmetry (NCS) | NCS oper:
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Details | The structure is a tetramer. Chains E, F, G, and H are portions of chains A, B, C, and D, respectively, that are modeled separately. |
-Components
#1: Protein | Mass: 74643.734 Da / Num. of mol.: 4 / Fragment: UNP residues 1-635,866-890 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: Protein/peptide | Mass: 1635.006 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) #3: Chemical | ChemComp-CMP / Sequence details | Chains E, F, G, and H are residues ~615 to ~633 (uncertain register) of chains A, B, C, and D. They ...Chains E, F, G, and H are residues ~615 to ~633 (uncertain register) of chains A, B, C, and D. They are represented as separate chains at the authors' request. | |
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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 hyperpolarization-activated cyclic nucleotide-gated ion channel in complex with cAMP Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Plasmid: pEG_BacMam |
Buffer solution | pH: 8 |
Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
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 FIELD / Nominal defocus max: 3300 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 1.78 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Symmetry | Point symmetry: C4 (4 fold cyclic) |
3D reconstruction | Resolution: 3.51 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 125339 / Symmetry type: POINT |