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Title | Cryo-electron microscopy unveils unique structural features of the human Kir2.1 channel. |
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Journal, issue, pages | Sci Adv, Vol. 8, Issue 38, Page eabq8489, Year 2022 |
Publish date | Sep 23, 2022 |
Authors | Carlos A H Fernandes / Dania Zuniga / Charline Fagnen / Valérie Kugler / Rosa Scala / Gérard Péhau-Arnaudet / Renaud Wagner / David Perahia / Saïd Bendahhou / Catherine Vénien-Bryan / |
PubMed Abstract | We present the first structure of the human Kir2.1 channel containing both transmembrane domain (TMD) and cytoplasmic domain (CTD). Kir2.1 channels are strongly inward-rectifying potassium channels ...We present the first structure of the human Kir2.1 channel containing both transmembrane domain (TMD) and cytoplasmic domain (CTD). Kir2.1 channels are strongly inward-rectifying potassium channels that play a key role in maintaining resting membrane potential. Their gating is modulated by phosphatidylinositol 4,5-bisphosphate (PIP). Genetically inherited defects in Kir2.1 channels are responsible for several rare human diseases, including Andersen's syndrome. The structural analysis (cryo-electron microscopy), surface plasmon resonance, and electrophysiological experiments revealed a well-connected network of interactions between the PIP-binding site and the G-loop through residues R312 and H221. In addition, molecular dynamics simulations and normal mode analysis showed the intrinsic tendency of the CTD to tether to the TMD and a movement of the secondary anionic binding site to the membrane even without PIP. Our results revealed structural features unique to human Kir2.1 and provided insights into the connection between G-loop and gating and the pathological mechanisms associated with this channel. |
External links | Sci Adv / PubMed:36149965 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.3 Å |
Structure data | EMDB-14678, PDB-7zdz: |
Chemicals | ChemComp-K: ChemComp-SR: |
Source |
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Keywords | MEMBRANE PROTEIN / Potassium channel / Inward-rectifier channel / inward rectification |