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Ion channel function of polycystin‐2/polycystin‐1 heteromer revealed by structure‐guided mutagenesis

12 May 2025

Abstract excerpt

Mutations in polycystin-1 (PC1) or polycystin-2 (PC2) cause autosomal-dominant polycystic kidney disease (ADPKD). Structural data suggest that one PC1 and three PC2 form heterotetrameric ion channels with an ion permeation pathway blocked by PC1 (R4100, R4107, and H4111) and PC2 (L677, N681) residues. Here, we demonstrate that replacing these residues with alanines results in a gain-of-function (GOF) PC2/PC1...

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PMID: 40353356
DOI: 10.1002/1873-3468.70059

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