7ZDZ

Cryo-EM structure of the human inward-rectifier potassium 2.1 channel (Kir2.1)

Summary for 7ZDZ

• Entry DOI: 10.2210/pdb7zdz/pdb
• EMDB information: 14678
• Descriptor: Inward rectifier potassium channel 2, POTASSIUM ION, STRONTIUM ION (3 entities in total)
• Functional Keywords: potassium channel, inward-rectifier channel, inward rectification, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 193590.90

Authors

Fernandes, C.A.H.,Venien-Bryan, C.,Fagnen, C.,Zuniga, D. (deposition date: 2022-03-30, release date: 2022-09-28, Last modification date: 2024-11-13)

Primary citation

Fernandes, C.A.H.,Zuniga, D.,Fagnen, C.,Kugler, V.,Scala, R.,Pehau-Arnaudet, G.,Wagner, R.,Perahia, D.,Bendahhou, S.,Venien-Bryan, C.
Cryo-electron microscopy unveils unique structural features of the human Kir2.1 channel.
Sci Adv, 8:eabq8489-eabq8489, 2022

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 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.

PubMed: 36149965
DOI: 10.1126/sciadv.abq8489

Experimental method

ELECTRON MICROSCOPY (4.3 Å)