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| Title | Bioactive lipid-mediated structural and functional regulation of the essential human potassium channel Kir7.1. |
|---|---|
| Journal, issue, pages | Nat Commun, Year 2026 |
| Publish date | Feb 11, 2026 |
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 / ![]() |
| PubMed 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. |
External links | Nat Commun / PubMed:41672996 |
| Methods | EM (single particle) |
| Resolution | 3.3 - 4.0 Å |
| Structure data | EMDB-71798, PDB-9pr5: EMDB-71799, PDB-9pr6: EMDB-71800, PDB-9pr7: |
| Chemicals | ![]() ChemComp-PIO: ![]() ChemComp-CLR: ![]() PDB-1cjg: |
| Source |
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Keywords | MEMBRANE PROTEIN / inwardly rectifying potassium channel Kir7.1 / KCNJ13 / electrophysiology / ion channels / steroids / steroid enantiomers |
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homo sapiens (human)
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