Extended Data Fig. 8: S6 sequence alignment and NALCN π-bulge.

a, Multi-sequence alignment from select ion channels. Residues that support the S6 π-bulge in NALCN are outlined with a purple box and dashed line indicates the observed hydrogen bond to the backbone carbonyl of the i-4 residue. Residues with side-chains that fill the NALCN pore fenestrations are outlined with a blue box, and residues with side-chains lining the closed S6-activation gate in NALCN are outlined with a green box. b, Side-view of S6 with polar side-chains supporting the π-bulge shown as stick with putative hydrogen bonds (dashed line) to the i-4 backbone carbonyls (*). c, Close-in view of the S6 π-bulges in NALCN. d, TRPV3 channel S6 in apo and ligand bound states (PDB: 6DVW and 6DVZ, respectively), with ___location of the π-bulge indicated.