Fig. 7: Hypotheses of regulatory activation in CCCs.
From: The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2
a The basic model of cation-chloride cotransporter activation. It is proposed that the inactive state is characterized by an inward-open TM conformation with CTDs in a tightly organized domain-swap configuration. On activation, the CTDs are released to a freely tethered configuration with accompanying change in the dimer architecture. b Our hypothesis is that NKCC activation occurs when the phosphorylated N terminus interacts with the CTD and disrupts the dimer. c The KCC inactive state exhibits an N terminus inhibitory peptide blocking the transport pore. Activation occurs when the peptide instead binds to the non-phosphorylated C terminus.
