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TitleCryo-EM structure of the human Kir7.1 channel reveals the molecular basis of snowflake vitreoretinal degeneration disease.
Journal, issue, pagesCommun Biol, Year 2026
Publish dateNov 28, 2025
AuthorsNiamh O'Malley / Chady Nasrallah / Ashton Churchill / Jay Bertrand / Belinda R Faust / B A Wallace /
PubMed AbstractThe inward rectifying human potassium channel 7.1 (Kir7.1) is a vital ion channel involved in maintaining cellular homoeostasis and electrical signalling across various tissues and organs, activated ...The inward rectifying human potassium channel 7.1 (Kir7.1) is a vital ion channel involved in maintaining cellular homoeostasis and electrical signalling across various tissues and organs, activated by phosphatidylinositol 4,5-bisphosphate (PIP). A genetically inherited loss-of-function mutation in Kir7.1 (R162W) has been linked to the rare retinal disease Snowflake Vitreoretinal Degeneration (SVD), for which there are currently no curative treatment options. Here, the cryo-EM structures of wild type Kir7.1 and the R162W disease-related variant are presented, which unveil the molecular basis of SVD: the reorientation of the mutant tryptophan side chains into the pore impedes the flow of potassium ions, which would result in the loss of Kir7.1 transport function. Furthermore, this investigation shows that PIP binding widens the helix bundle crossing gate diameter, even in the absence of a docked cytoplasmic domain. This observation contrasts with other Kir-PIP₂ complexes and suggests that Kir7.1 may adopt an intermediate conformation during channel activation. These findings provide a structural basis for Kir7.1 loss of function in SVD and provide a framework for future therapeutic development.
External linksCommun Biol / PubMed:42324408
MethodsEM (single particle)
Resolution3.29 - 3.6 Å
Structure data

55878

9tfv

EMDB-55878, PDB-9tfv:
Cryo-EM structure of the inward rectifying potassium channel 7.1 (Kir7.1)
Method: EM (single particle) / Resolution: 3.6 Å

55889

9tg3

EMDB-55889, PDB-9tg3:
Cryo-EM structure of the R162W mutant inward rectifying potassium channel 7.1 (Kir7.1)
Method: EM (single particle) / Resolution: 3.5 Å

55892

9tg6

EMDB-55892, PDB-9tg6:
Cryo-EM structure of the inward rectifying potassium channel 7.1 (Kir7.1) in complex with PIP2
Method: EM (single particle) / Resolution: 3.29 Å

Chemicals

ChemComp-K:
Unknown entry

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

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / potassium ion channel / active conformation / human membrane protein

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