[English] 日本語
Yorodumi
- EMDB-35195: Rat Kir4.1 in complex with PIP2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-35195
TitleRat Kir4.1 in complex with PIP2
Map data
Sample
  • Complex: Rat Kir4.1 in complex with PIP2
    • Protein or peptide: ATP-sensitive inward rectifier potassium channel 10
  • Ligand: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate
Keywordskir4.1 / ion channel / transport protein / MEMBRANE PROTEIN
Function / homology
Function and homology information


glutamate reuptake / Potassium transport channels / L-glutamate import / response to blue light / response to mineralocorticoid / central nervous system myelination / regulation of resting membrane potential / oligodendrocyte development / cellular response to potassium ion / astrocyte projection ...glutamate reuptake / Potassium transport channels / L-glutamate import / response to blue light / response to mineralocorticoid / central nervous system myelination / regulation of resting membrane potential / oligodendrocyte development / cellular response to potassium ion / astrocyte projection / inward rectifier potassium channel activity / potassium ion homeostasis / regulation of monoatomic ion transmembrane transport / non-motile cilium assembly / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / membrane hyperpolarization / adult walking behavior / optic nerve development / ciliary base / potassium ion import across plasma membrane / microvillus / monoatomic ion channel complex / potassium channel activity / response to glucocorticoid / potassium ion transmembrane transport / visual perception / regulation of membrane potential / establishment of localization in cell / regulation of long-term neuronal synaptic plasticity / potassium ion transport / presynapse / cell body / basolateral plasma membrane / apical plasma membrane / signaling receptor binding / ATP binding / identical protein binding / plasma membrane
Similarity search - Function
Potassium channel, inwardly rectifying, Kir1.2 / Potassium channel, inwardly rectifying, transmembrane domain / Inward rectifier potassium channel transmembrane domain / Potassium channel, inwardly rectifying, Kir, cytoplasmic / Potassium channel, inwardly rectifying, Kir / Inward rectifier potassium channel, C-terminal / Inward rectifier potassium channel C-terminal domain / Immunoglobulin E-set
Similarity search - Domain/homology
ATP-sensitive inward rectifier potassium channel 10
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.85 Å
AuthorsZhao C / Guo J
Funding support China, 1 items
OrganizationGrant numberCountry
Ministry of Education (MoE, China)Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University China
CitationJournal: Nat Chem Biol / Year: 2024
Title: Pharmacological inhibition of Kir4.1 evokes rapid-onset antidepressant responses.
Authors: Xiaoyu Zhou / Cheng Zhao / Haiyan Xu / Yixiang Xu / Li Zhan / Pei Wang / Jingyi He / Taotao Lu / Yueling Gu / Yan Yang / Chanjuan Xu / Yiyang Chen / Yuxuan Liu / Yue Zeng / Fuyun Tian / Qian ...Authors: Xiaoyu Zhou / Cheng Zhao / Haiyan Xu / Yixiang Xu / Li Zhan / Pei Wang / Jingyi He / Taotao Lu / Yueling Gu / Yan Yang / Chanjuan Xu / Yiyang Chen / Yuxuan Liu / Yue Zeng / Fuyun Tian / Qian Chen / Xin Xie / Jianfeng Liu / Hailan Hu / Jian Li / Yueming Zheng / Jiangtao Guo / Zhaobing Gao /
Abstract: Major depressive disorder, a prevalent and severe psychiatric condition, necessitates development of new and fast-acting antidepressants. Genetic suppression of astrocytic inwardly rectifying ...Major depressive disorder, a prevalent and severe psychiatric condition, necessitates development of new and fast-acting antidepressants. Genetic suppression of astrocytic inwardly rectifying potassium channel 4.1 (Kir4.1) in the lateral habenula ameliorates depression-like phenotypes in mice. However, Kir4.1 remains an elusive drug target for depression. Here, we discovered a series of Kir4.1 inhibitors through high-throughput screening. Lys05, the most potent one thus far, effectively suppressed native Kir4.1 channels while displaying high selectivity against established targets for rapid-onset antidepressants. Cryogenic-electron microscopy structures combined with electrophysiological characterizations revealed Lys05 directly binds in the central cavity of Kir4.1. Notably, a single dose of Lys05 reversed the Kir4.1-driven depression-like phenotype and exerted rapid-onset (as early as 1 hour) antidepressant actions in multiple canonical depression rodent models with efficacy comparable to that of (S)-ketamine. Overall, we provided a proof of concept that Kir4.1 is a promising target for rapid-onset antidepressant effects.
History
DepositionJan 26, 2023-
Header (metadata) releaseFeb 28, 2024-
Map releaseFeb 28, 2024-
UpdateOct 16, 2024-
Current statusOct 16, 2024Processing site: PDBj / Status: Released

-
Structure visualization

Supplemental images

emd_35195.png

Downloads & links

-
Map

FileDownload / File: emd_35195.map.gz / Format: CCP4 / Size: 22.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.88 Å/pix.
x 128 pix.
= 240.64 Å		1.88 Å/pix.
x 128 pix.
= 240.64 Å		1.88 Å/pix.
x 128 pix.
= 240.64 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel size
XYZ
EMDB info.1.0141.0141.014
CCP4 map header1.881.881.88
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0137
Minimum - Maximum-0.027175736 - 0.069874756
Average (Standard dev.)-0.0000069376683 (±0.0034323353)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions180180180
Spacing180180180
CellA=B=C: 182.52 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_35195_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Rat Kir4.1 in complex with PIP2

EntireName: Rat Kir4.1 in complex with PIP2
Components
  • Complex: Rat Kir4.1 in complex with PIP2
    • Protein or peptide: ATP-sensitive inward rectifier potassium channel 10
  • Ligand: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate

-
Supramolecule #1: Rat Kir4.1 in complex with PIP2

SupramoleculeName: Rat Kir4.1 in complex with PIP2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Rattus norvegicus (Norway rat)

-
Macromolecule #1: ATP-sensitive inward rectifier potassium channel 10

MacromoleculeName: ATP-sensitive inward rectifier potassium channel 10 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Rattus norvegicus (Norway rat)
Molecular weightTheoretical: 38.791723 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GAPGIRRRRV LTKDGRSNVR MEHIADKRFL YLKDLWTTFI DMQWRYKLLL FSATFAGTWF LFGVVWYLVA VAHGDLLELG PPANHTPCV VQVHTLTGAF LFSLESQTTI GYGFRYISEE CPLAIVLLIA QLVLTTILEI FITGTFLAKI ARPKKRAETI R FSQHAVVA ...String:
GAPGIRRRRV LTKDGRSNVR MEHIADKRFL YLKDLWTTFI DMQWRYKLLL FSATFAGTWF LFGVVWYLVA VAHGDLLELG PPANHTPCV VQVHTLTGAF LFSLESQTTI GYGFRYISEE CPLAIVLLIA QLVLTTILEI FITGTFLAKI ARPKKRAETI R FSQHAVVA YHNGKLCLMI RVANMRKSLL IGCQVTGKLL QTHQTKEGEN IRLNQVNVTF QVDTASDSPF LILPLTFYHV VD ETSPLKD LPLRSGEGDF ELVLILSGTV ESTSATCQVR TSYLPEEILW GYEFTPAISL SASGKYVADF SLFDQVVKVA SPG GLRDST VRYGDPEKLK LDYKDDDDK

UniProtKB: ATP-sensitive inward rectifier potassium channel 10

-
Macromolecule #2: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(o...

MacromoleculeName: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate
type: ligand / ID: 2 / Number of copies: 4 / Formula: PIO
Molecular weightTheoretical: 746.566 Da
Chemical component information

ChemComp-PIO:
[(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 62.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: DARK FIELD / Nominal defocus max: 1.4000000000000001 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

6xit

Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.85 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 22786
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

+
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