Residue conservation among Slo family members. (A) Aplysia (aSlo1) sequence is compared with human and mouse Slo3 and Slo1. Residues identical in all species are gray; mammalian Slo1 residues shared with aSlo1 and perhaps one Slo3 sequence are in yellow; residues shared with Slo3 are in cyan; residues unique to aSlo1 are in red. Note the strong conservation of aSlo1 with mSlo1 through the first part of RCK1 and also surrounding the Ca²⁺ bowl region. In S0–S6, many more residues unique to aSlo1 are found, most notably more cytosolic part of S4 and also much of S5 and S6. Much of aSlo1 S0 is also poorly conserved. (B) The same color coding is mapped onto the Aplysia liganded S0–S6 structure, again highlighting the large number of residues unique to aSlo1. Important residues shared among Slo3, aSlo1, and mammalian Slo1 include mR207, mR210, and mR213. (C) Extent of conservation is mapped onto the RCK1 domain. In this case, aSlo1 shares strong identity with much of the mammalian sequences in the vicinity of the ligand-binding structures. (D) Elements of RCK2 near the Ca²⁺ bowl motif are highly conserved between aSlo1 and mammalian Slo1.