Fig. 2: A closed pore with an elongated intracellular gate.
From: Structural basis for Ca2+ activation of the heteromeric PKD1L3/PKD2L1 channel
a Difference in the architecture of PD between PKD1L3/2L1 and PKD1/2 (PDB code: 6A70). PKD1L3 has a conventional PH1-SF-PH2 segment that is missing in PKD134. Inset: Comparison of the PD segments of PKD1 (yellow) and PKD1L3 (blue). The S6 segment of PKD1 bends in the middle, resulting in a S6a half helix that aligns with a typical pore helix PH1. The sequence connecting S6a and S5 is invisible in PKD1. b Conformational shifts between the S6 tetrahelical bundles of PKD1L3/2L1 and PKD1/2. The PD of apo PKD1L3/2L1 is superimposed with that of PKD1/2. A secondary structural element transition in the middle of S6 from an α helical turn in PKD2L1 to a π helix in PKD2 results in an iris-like rotation of the S6 tetrahelical bundle. The conformational shifts of the corresponding segments from PKD1L3/2L1 to PKD1/2 are indicated by red arrows. c The PD is sealed by an elongated intracellular gate. The permeation path of the apo heterotetramer, calculated by HOLE69, is illustrated by gray dots. The pore radii of PKD1L3/2L1 (red), homotetrameric PKD2L1 (blue, PDB code: 5Z1W), and homotetrameric PKD2 (green, PDB code: 5T4D) are compared (right). The intracellular gate of PKD1L3/2L1 is extraordinarily elongated and will be illustrated as two layers. Right two panels: Composition of the two layers of the intracellular gate. Shown here are extracellular views. The densities are contoured at 5 σ. d PD comparison between PKD1L3/2L1 and PKD2L1 homotetramer. Longer S6 segments of PKD2L1 were resolved in PKD1L3/2L1 than those in the PKD2L1 homotetramer. Note that the PKD2L1 subunits exhibit nearly identical conformations in the two channels. e Structural deviations of the S4–S5 linkers of the four subunits in PKD1L3/2L1. Left: Whereas the linkers between S4 and S5 in PKD2L1, similar to those in other VGIC proteins, forms a short helix, that in PKD1L3 is a loop. Even among the three PKD2L1 subunits, the S4–S5 linker in VSDIII is distinct from the other two. The C-terminal short helix (dark green) of the S4–S5III bends toward the PD, pushing S6 of PKD1L3 inward. Right: The S4–S5 helix of PKD2L1-III interacts with the S5 and S6 helices of PKD1L3 through specific hydrogen bonds (upper panel) and extensive van der Waals contacts (lower panel). The hydrogen bonds are indicated by black dashed lines.
