1.A.5.1.3
Heteromeric polycystic kidney disease proteins 1 and 2-like 1 (PKD1L1/PKD2L1/PC2) cation (calcium) channel of kidney primary cilia (DeCaen et al. 2013).  PKD2L1 is probably orthologous to mouse TC# 1.A.5.2.2. The voltage dependence of PKD2L1 may reflect the charge state of the S4 domain (Numata et al. 2017). PKD2L1, (TRPP3) is involved in the sour sensation and other pH-dependent processes and is a nonselective cation channel that can be regulated by voltage, protons, and calcium. The 3-d structure has been determined by cryoEM at 3.4 Å resolution (Su et al. 2018). Unlike its ortholog PKD2, the pore helix and TMS6, which are involved in upper and lower-gate opening, adopt an open conformation. The pore domain dilation is coupled to conformational changes of voltage-sensing domains via a series of pi-pi interactions, suggesting a potential PKD2L1 gating mechanism (Su et al. 2018). Autosomal dominant polycystic kidney disease is caused by mutations in PKD1 or PKD2 genes; the latter encodes polycystin-2 (PC2, also known as TRPP2), a member of the transient receptor potential (TRP) ion channel family. Despite most pathogenic mutations in PKD2 being truncation variants, there are many point mutations, which cause small changes in protein sequences but dramatic changes in the in vivo function of PC2. Conformational consequences of these mutations based on the cryo-EM structures of PC2 provide insight into the structure and function of PC2 and the molecular mechanism of pathogenesis caused by these mutations (Wang et al. 2023). Polycystin-1 interacting protein-1 (CU062) interacts with the ectodomain of polycystin-1 (PC1) (Lea et al. 2023).