Fig. 4. Voltage sensors of NALCN at the depolarized state.

a Sequence alignment of S2 and S4 segments. The sequences of rat NALCN, human NALCN, fruit fly NCA, nematode NCA1, NCA2, human Ca_V3.1, rabbit Ca_V1.1, human Na_V1.2, and human Na_V1.4 were aligned using PROMALS3D⁵³. Residues forming the charge-transfer center are shaded in gray. The conserved negative or polar E1 and E4 on S2 segments, F3 on S2 segments, and positive R1-R6 on S4 segments are highlighted in red, brown, and blue, respectively. b Structures of four VSDs in NALCN. Gating charges and charge-transfer center residues are shown as sticks. 3₁₀ helices are colored in pink.