Fig. 1: The PKD1L3-CTD/PKD2L1 heterocomplex retains Ca²⁺ and acid-induced channel activity.

a Topology diagram of PKD1L3 and PKD2L1. PKD1L3, and PKD2L1 proteins assemble to a heterocomplex with a stoichiometric ratio of 1:3. The constructs used for structural determination in this study, mouse PKD1L3-CTD (residues 1632–2151) and PKD2L1 (residues 64–629), are indicated by the dashed box. CTL C-type lectin ___domain, REJ sperm receptor for egg jelly, PLAT Polycystin-1, Lipoxygenase, α-toxin ___domain, PMD polycystin-mucolipin ___domain, PD pore ___domain, VSD voltage-sensing ___domain. b The Ca²⁺ and acid-induced channel activity of the PKD1L3-CTD/PKD2L1 heterocomplex is similar to that of the full-length (FL) channel. The Ca²⁺ and acid-induced currents were recorded from Xenopus oocytes expressing either full-length PKD1L3 or PKD1L3-CTD with PKD2L1. Shown here are representative traces for gap-free recording at −80 mV. c Scatter plots and bar graphs of the Ca²⁺-induced currents at −80 mV recorded from oocytes expressing the indicated proteins. The number of oocytes is shown below each bar. Data are presented as mean ± SD in the bar graph. Currents in each group are compared with that of PKD1L3-FL/2L1-injected group with two-sided Student’s t test. n.s.: not significant; ****P < 0.0001. d The side (left) and intracellular (right) views of the cryo-EM structure of the PKD1L3-CTD/PKD2L1 complex. For simplicity, we will call it PKD1L3/2L1. The glycosyl moieties are shown as sticks. The black and red arrows highlight the different structures of the S4–S5 linkers in PKD1L3 and the three PKD2L1 subunits, respectively. e Structural comparison of PKD1L3/2L1 with and without added Ca²⁺. The two structures will be referred to as “Ca²⁺-loaded” and “apo”. All structural figures were prepared in UCSF chimera⁶⁵ if not otherwise indicated.