Structural characterizations of PKD2L1. a General topology of PKD2L1. PKD2 has a similar topology with a longer N-terminus and no oligomerization domain (OD). b Overall EM map of PKD2L1 (residues 64–629) colored according to different protomers. A swap structure feature can be visualized. Shown from the side view. c, d Overall structure of PKD2L1 (residues 64–629), view from the side and top, respectively. The structure is domain-colored as in panel a. The same color scheme was applied throughout the structural analysis in Figs. 1–, Supplementary Figs. and , and Supplementary Movies –. Glycosyl moieties are shown as sticks. All the above structure figures were prepared using PyMol (The PyMOL Molecular Graphics System, Version 1.8 Schrödinger, LLC.) and the EM map was generated using UCSF Chimera. e, f Ca2+ response ICa was elicited when [Ca2+]o rapidly switched from 0 to 100 mM (green bar). Exemplar traces (e) for PKD2L1_WT (left) or PKD2L1_64–629 (right), both in complex with PKD1L3. Statistical summaries of ICa (f) for the peak amplitude, and the time constant of the decay phase (Td). Number of cells for each group are indicated in the parentheses. PKD2L1_64–629 represents the truncated version of PKD2L1: 64–629, from which the Cryo-EM structure was resolved. g, h Acid response (IpH) was induced when the stimulus of pH 2.5 (red bar) was quickly withdrawn. In all, 2 mM [Ca2+]o was included in the bath solution for IpH throughout this study. Exemplar traces (g) for PKD2L1_WT (left) or PKD2L1_64–629 (right), both in complex with PKD1L3. Statistical summaries of IpH (h) for the peak amplitude, and the time constant of the decay phase (Td). Intracellular buffer of 0.5 mM EGTA was used throughout. All above values are in mean ± SEM, indicated with significance (*p < 0.05; **p < 0.01; and ***p < 0.001). More detailed studies including the negative control can be found in our previous paper