Current structural view on potassium chloride co-transporters

Abstract Cation chloride co-transporters (CCC) play an essential role for neuronal chloride homeostasis. CCC includes K+ Cl− outward co-transporters (KCCs) and Na+ K+ Cl− inward co-transporters (NKCCs). Although NKCCs and KCCs co-transporters have been studied intensively for several decades, a full picture of their common structural determinants and structure/function differences is still missing. A recent molecular architecture of KCC2 has been reported. This structure will be described and compared to high resolution structures of related co-transporters NKCC1 and KCC1 as well as previously reported biochemical and bioinformation information. Thus, the aim of this chapter is to provide a comprehensive overview of our current understanding of the architecture-function relationships of NKCCs and KCCs co-transporters. Differential cell expression profiles, sequence alignment, secondary structure prediction, structural comparison analysis, post-translational modification and oligomerization provide explanation of the subcellular and molecular organization and function of KCCs and NKCCs. This knowledge will enable structure-guided drug discovery allowing to meet many currently unmet medical needs related to neurological disorders and other human diseases.