Energetic landscape of polycystin channel gating.

ABSTRACT: Members of the polycystin family (PKD2 and PKD2L1) of transient receptor potential (TRP) channels conduct Ca²⁺ and depolarizing monovalent cations. Variants in PKD2 cause autosomal dominant polycystic kidney disease (ADPKD) in humans, whereas loss of PKD2L1 expression causes seizure susceptibility in mice. Understanding structural and functional regulation of these channels will provide the basis for interpreting their molecular dysregulation in disease states. However, the complete structures of polycystins are unresolved, as are the conformational changes regulating their conductive states. To provide a holistic understanding of the polycystin gating cycle, we use computational prediction tools to model missing PKD2L1 structural motifs and evaluate more than 150 mutations in a

SUBMITTER: Ng LC 

PROVIDER: S-EPMC10328073 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature