[English] 日本語
Yorodumi
- PDB-5u6p: Structure of the human HCN1 hyperpolarization-activated cyclic nu... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5u6p
TitleStructure 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
KeywordsTRANSPORT 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 / 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
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 ...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
ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE / Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.51 Å
AuthorsLee, C.-H. / MacKinnon, R.
CitationJournal: 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
DepositionDec 8, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 25, 2017Provider: repository / Type: Initial release
Revision 1.1Sep 27, 2017Group: Author supporting evidence / Data collection / Category: em_image_scans / pdbx_audit_support
Revision 1.2Mar 13, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-8512
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 11
E: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 11
B: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 11
F: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 11
C: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 11
G: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 11
D: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 11
H: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 11
hetero molecules


Theoretical massNumber of molelcules
Total (without water)306,43212
Polymers305,1158
Non-polymers1,3174
Water0
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_5551
Noncrystallographic symmetry (NCS)NCS oper:
IDCodeMatrixVector
1given(1), (1), (1)
2given(-0.007682, 0.999958, -0.005088), (-0.999966, -0.007696, -0.002854), (-0.002893, 0.005066, 0.999983)0.52019, 122.84318, -0.20262
3given(-0.999982, -0.00533, -0.002917), (0.005334, -0.999985, -0.001227), (-0.00291, -0.001242, 0.999995)122.48782, 121.97884, 0.20527
4given(0.008326, -0.99995, -0.005461), (0.999964, 0.008335, -0.001634), (0.00168, -0.005447, 0.999984)121.74802, -0.28717, 0.1402
DetailsThe 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
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 11 / Brain cyclic nucleotide-gated channel 1 / BCNG-1


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
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 11 / Brain cyclic nucleotide-gated channel 1


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 / ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE / CYCLIC AMP / CAMP / Cyclic adenosine monophosphate


Mass: 329.206 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Formula: C10H12N5O6P
Sequence detailsChains 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.

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Human HCN1 hyperpolarization-activated cyclic nucleotide-gated ion channel in complex with cAMP
Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1-#2 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human) / Plasmid: pEG_BacMam
Buffer solutionpH: 8
SpecimenConc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: GOLD / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 3300 nm / Nominal defocus min: 1500 nm
Image recordingElectron dose: 1.78 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C4 (4 fold cyclic)
3D reconstructionResolution: 3.51 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 125339 / Symmetry type: POINT

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more