Fig. 3: A Lys switch for Ca²⁺ entrance to the “KDDD” selectivity filter (SF).

a An asymmetric SF. Left: The pore domain of the apo and Ca²⁺-loaded complexes exhibits nearly identical overall conformation. Right: The distinct composition of the SF segments in PKD1L3 and PKD2L1 results in an asymmetric SF in the heterotetramer. Shown in the insets are the side views of the SF in the two diagonal subunits of the apo structure. b A Ca²⁺ ion is found in the SF in the Ca²⁺-loaded structure. Left: Ca²⁺ is positioned off the central axis and closer to PKD1L3. Shown here is an extracellular view of the PD. Right: The bound Ca²⁺ ion is mainly coordinated by three carbonyl oxygen groups on the SF loop of PKD1L3. The carboxylate group of Asp523 and two carbonyl oxygens from the two preceding residues in PKD2L3-III may also contribute to water-mediated coordination. The distances are indicated as black dashed lines and labeled in unit Å. c The upper site of the SF is open for Ca²⁺ entry with an outward swing of the long side chain of Lys2069. Left: Distinct conformations of Lys2069 between the apo (pink) and the Ca²⁺-loaded (domain colored) structures. Right: The Ca²⁺ was clearly resolved in the map of Ca²⁺-loaded complex. The densities, shown as gray mesh, are contoured at 4 σ. d An enlarged outer mouth and redistributed surface charges of the SF upon addition of Ca²⁺. Shown here are extracellular views of the electrostatic surface potential of the PD calculated in PyMol⁷⁰.