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- EMDB-71800: Cryo-EM structure of the human inward-rectifier potassium 7.1 cha... -

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Basic information

Entry
Database: EMDB / ID: EMD-71800
TitleCryo-EM structure of the human inward-rectifier potassium 7.1 channel (Kir7.1) with enantiomer of 17-hydroxyprogesterone caproate
Map data
Sample
  • Complex: human inward-rectifier potassium 7.1 channel (Kir7.1) with enantiomer of 17-hydroxyprogesterone caproate
    • Protein or peptide: Inward rectifier potassium channel 13
  • 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
  • Ligand: (13xi,17xi)-3,20-dioxo-10xi,14beta-pregn-4-en-17-yl hexanoate
Keywordsinwardly rectifying potassium channel Kir7.1 / KCNJ13 / electrophysiology / ion channels / steroids / steroid enantiomers / MEMBRANE PROTEIN
Function / homology
Function and homology information


regulation of monoatomic ion transmembrane transport / inward rectifier potassium channel activity / potassium ion import across plasma membrane / monoatomic ion channel complex / potassium ion transport / plasma membrane
Similarity search - Function
Inward rectifier potassium channel 13 / 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
Inward rectifier potassium channel 13
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.0 Å
AuthorsNiu Q / Vu S / Zhang R / Fu Z / Lishko PV
Funding support United States, 1 items
OrganizationGrant numberCountry
Other private United States
CitationJournal: Nat Commun / Year: 2026
Title: Bioactive lipid-mediated structural and functional regulation of the essential human potassium channel Kir7.1.
Authors: Qingwei Niu / Simon Vu / Yuanjiang Xu / Mingxing Qian / Anastasiia Rudenko / Jin Ye / Jianwei Zeng / Wei Huang / Douglas F Covey / Rui Zhang / Ziao Fu / Polina V Lishko /
Abstract: The inwardly rectifying potassium channel Kir7.1 is essential for the physiological function of diverse tissues, including the retinal pigment epithelium and the gestational myometrium. Loss-of- ...The inwardly rectifying potassium channel Kir7.1 is essential for the physiological function of diverse tissues, including the retinal pigment epithelium and the gestational myometrium. Loss-of-function mutations in KCNJ13, which encodes Kir7.1, or conditional ablation of Kir7.1 in the retinal pigment epithelium, lead to early-onset vision loss. Despite strong genetic evidence supporting Kir7.1 as a therapeutic target, its regulation by endogenous ligands-beyond phosphoinositides-remains poorly understood. Here, we report cryo-electron microscopy structures of human Kir7.1 in multiple functional states at resolutions ranging from 2.8 Å to 4.0 Å. These structures uncover the molecular basis of Kir7.1 modulation by PIP, its selectivity, rectification, and identify a distinct steroid-binding site that may mediate cooperative channel gating. Our data suggest that endogenous cholesterol acts as an inhibitory ligand, which is displaced by select activating steroids. These activating steroids work in concert with PIP to promote channel opening through profound changes in cytoplasmic domains, and the linker region. Electrophysiological analyses define a pharmacological landscape of Kir7.1 activators, providing innovative tools to probe and modulate channel function in both physiological and pathological contexts.
History
DepositionJul 23, 2025-
Header (metadata) releaseFeb 25, 2026-
Map releaseFeb 25, 2026-
UpdateFeb 25, 2026-
Current statusFeb 25, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_71800.png

Downloads & links

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Map

FileDownload / File: emd_71800.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

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AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 320 pix.
= 233.728 Å		0.73 Å/pix.
x 320 pix.
= 233.728 Å		0.73 Å/pix.
x 320 pix.
= 233.728 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.7304 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.15
Minimum - Maximum-0.019739391 - 2.4191225
Average (Standard dev.)0.002092379 (±0.031654283)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 233.72801 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_71800_msk_1.map
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Additional map: #2

Fileemd_71800_additional_1.map
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Additional map: #1

Fileemd_71800_additional_2.map
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Half map: #2

Fileemd_71800_half_map_1.map
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Half map: #1

Fileemd_71800_half_map_2.map
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Sample components

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Entire : human inward-rectifier potassium 7.1 channel (Kir7.1) with enanti...

EntireName: human inward-rectifier potassium 7.1 channel (Kir7.1) with enantiomer of 17-hydroxyprogesterone caproate
Components
  • Complex: human inward-rectifier potassium 7.1 channel (Kir7.1) with enantiomer of 17-hydroxyprogesterone caproate
    • Protein or peptide: Inward rectifier potassium channel 13
  • 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
  • Ligand: (13xi,17xi)-3,20-dioxo-10xi,14beta-pregn-4-en-17-yl hexanoate

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Supramolecule #1: human inward-rectifier potassium 7.1 channel (Kir7.1) with enanti...

SupramoleculeName: human inward-rectifier potassium 7.1 channel (Kir7.1) with enantiomer of 17-hydroxyprogesterone caproate
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 160 KDa

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Macromolecule #1: Inward rectifier potassium channel 13

MacromoleculeName: Inward rectifier potassium channel 13 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 40.569453 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDSSNCKVIA PLLSQRYRRM VTKDGHSTLQ MDGAQRGLAY LRDAWGILMD MRWRWMMLVF SASFVVHWLV FAVLWYVLAE MNGDLELDH DAPPENHTIC VKYITSFTAA FSFSLETQLT IGYGTMFPSG DCPSAIALLA IQMLLGLMLE AFITGAFVAK I ARPKNRAF ...String:
MDSSNCKVIA PLLSQRYRRM VTKDGHSTLQ MDGAQRGLAY LRDAWGILMD MRWRWMMLVF SASFVVHWLV FAVLWYVLAE MNGDLELDH DAPPENHTIC VKYITSFTAA FSFSLETQLT IGYGTMFPSG DCPSAIALLA IQMLLGLMLE AFITGAFVAK I ARPKNRAF SIRFTDTAVV AHMDGKPNLI FQVANTRPSP LTSVRVSAVL YQERENGKLY QTSVDFHLDG ISSDECPFFI FP LTYYHSI TPSSPLATLL QHENPSHFEL VVFLSAMQEG TGEICQRRTS YLPSEIMLHH CFASLLTRGS KGEYQIKMEN FDK TVPEFP TPLVSKSPNR TDLDIHINGQ SIDNFQISET GLTE

UniProtKB: Inward rectifier potassium channel 13

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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

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Macromolecule #3: (13xi,17xi)-3,20-dioxo-10xi,14beta-pregn-4-en-17-yl hexanoate

MacromoleculeName: (13xi,17xi)-3,20-dioxo-10xi,14beta-pregn-4-en-17-yl hexanoate
type: ligand / ID: 3 / Number of copies: 4 / Formula: A1CJG
Molecular weightTheoretical: 428.604 Da

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5 / Details: 20mM Tris-HCl pH 7.5, 150 mM KCl, 0.02% GDN
GridModel: UltrAuFoil R0./1 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 45 sec. / Pretreatment - Atmosphere: AIR / Details: Pelco easiGlow
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number real images: 12187 / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.6 µm / Nominal magnification: 165000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 4004877
CTF correctionSoftware - Name: cryoSPARC / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER / Details: CryoSPARC ab initio
Final reconstructionNumber classes used: 1 / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 75599
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final 3D classificationSoftware - Name: cryoSPARC

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Atomic model buiding 1

Initial modelChain - Source name: AlphaFold / Chain - Initial model type: in silico model
RefinementProtocol: BACKBONE TRACE
Output model

PDB-9pr7:
Cryo-EM structure of the human inward-rectifier potassium 7.1 channel (Kir7.1) with enantiomer of 17-hydroxyprogesterone caproate

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