Fig. 6: Dimeric interface of hNKCC1 and mKCC2.

a–d Schematic representation of the TMD dimer architecture between different transporters (Adic (yellow), hNKCC1 (blue), mKCC2 (brown), and hKCC1 (green)) with TM11-12 shown as ribbons and other TMD regions shown as surface representation. e The NKCC1 homodimer is stabilized by hydrogen bond interaction between Y751 in TM12 of one monomer with H695 in TM10 of the other; in addition, there are stabilizing hydrophobic interactions between TM11-12 hairpins (labeled residues). f Homodimeric oxidative crosslinking of NKCC1 with single cysteine substitutions in TM 11-12. Cells were treated with (+) or without (−) cupric phenanthroline before lysis. g The W732C mutant exhibits about 25% of the Rb⁺ influx activity of wild-type NKCC1. Transport activity is largely restored in W732C after a 30 min pretreatment with 40 mM DTT to break the disulfide linkage between hNKCC1 monomers; mean ± SEM. h Cytoplasmic-domain dimeric interactions in mKCC2. D775, Q782, and S783 from one subunit (brown) form hydrogen bonds with Q766, I769, and S771 from the neighboring subunit (blue) to stabilize the dimer.