[English] 日本語
Yorodumi
- PDB-8inz: Cryo-EM structure of human HCN3 channel in apo state -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8inz
TitleCryo-EM structure of human HCN3 channel in apo state
ComponentsPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
KeywordsMEMBRANE PROTEIN / human HCN3 channel
Function / homology
Function and homology information


cone cell pedicle / HCN channels / HCN channel complex / regulation of membrane depolarization / cellular response to dopamine / voltage-gated sodium channel activity / voltage-gated potassium channel activity / sodium ion transmembrane transport / cAMP binding / potassium ion transmembrane transport ...cone cell pedicle / HCN channels / HCN channel complex / regulation of membrane depolarization / cellular response to dopamine / voltage-gated sodium channel activity / voltage-gated potassium channel activity / sodium ion transmembrane transport / cAMP binding / potassium ion transmembrane transport / regulation of membrane potential / axon / neuronal cell body / dendrite / plasma membrane
Similarity search - Function
: / Ion transport N-terminal / Ion transport protein N-terminal / Potassium channel, voltage-dependent, EAG/ELK/ERG / 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 N-terminal / Ion transport protein N-terminal / Potassium channel, voltage-dependent, EAG/ELK/ERG / 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
: / Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.72 Å
AuthorsYu, B. / Lu, Q.Y. / Li, J. / Zhang, J.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J Biol Chem / Year: 2024
Title: Cryo-EM structure of human HCN3 channel and its regulation by cAMP.
Authors: Bo Yu / Qiuyuan Lu / Jian Li / Xinyu Cheng / Han Hu / Yuanshuo Li / Tong Che / Yaoguang Hua / Haihai Jiang / Yuting Zhang / Cuiling Xian / Tingting Yang / Ying Fu / Yixiang Chen / Weiwei Nan ...Authors: Bo Yu / Qiuyuan Lu / Jian Li / Xinyu Cheng / Han Hu / Yuanshuo Li / Tong Che / Yaoguang Hua / Haihai Jiang / Yuting Zhang / Cuiling Xian / Tingting Yang / Ying Fu / Yixiang Chen / Weiwei Nan / Peter J McCormick / Bing Xiong / Jingjing Duan / Bo Zeng / Yanyan Li / Yang Fu / Jin Zhang /
Abstract: HCN channels are important for regulating heart rhythm and nerve activity and have been studied as potential drug targets for treating depression, arrhythmia, nerve pain, and epilepsy. Despite ...HCN channels are important for regulating heart rhythm and nerve activity and have been studied as potential drug targets for treating depression, arrhythmia, nerve pain, and epilepsy. Despite possessing unique pharmacological properties, HCN channels share common characteristics in that they are activated by hyperpolarization and modulated by cAMP and other membrane lipids. However, the mechanisms of how these ligands bind and modulate HCN channels are unclear. In this study, we solved structures of full-length human HCN3 using cryo-EM and captured two different states, including a state without any ligand bound and a state with cAMP bound. Our structures reveal the novel binding sites for cholesteryl hemisuccinate in apo state and show how cholesteryl hemisuccinate and cAMP binding cause conformational changes in different states. These findings explain how these small modulators are sensed in mammals at the molecular level. The results of our study could help to design more potent and specific compounds to influence HCN channel activity and offer new therapeutic possibilities for diseases that lack effective treatment.
History
DepositionMar 10, 2023Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Apr 10, 2024Provider: repository / Type: Initial release
Revision 1.1Jul 10, 2024Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
C: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
A: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
B: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
D: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)346,5438
Polymers344,5724
Non-polymers1,9714
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3


Mass: 86142.922 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HCN3
Production host: Mammalian expression vector BsrGI-MCS-pcDNA3.1 (others)
References: UniProt: Q9P1Z3
#2: Chemical
ChemComp-VX9 / 4-[[(2~{S},4~{a}~{R},6~{S},8~{a}~{S})-6-[(4~{S},5~{R})-4-[(2~{S})-butan-2-yl]-5,9-dimethyl-decyl]-4~{a}-methyl-2,3,4,5,6,7,8,8~{a}-octahydro-1~{H}-naphthalen-2-yl]oxy]-4-oxidanylidene-butanoic acid


Mass: 492.774 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C31H56O4 / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Mammalian expression vector BsrGI-MCS-pcDNA3.1 (others)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
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 FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 1800 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.72 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 71465 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00615328
ELECTRON MICROSCOPYf_angle_d1.21520844
ELECTRON MICROSCOPYf_dihedral_angle_d11.0948896
ELECTRON MICROSCOPYf_chiral_restr0.1572388
ELECTRON MICROSCOPYf_plane_restr0.0072552

+
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://pdbjlc1.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