Structural dynamics and regulation of the mammalian SLC9A family of Na⁺/H⁺ exchangers.

摘要: Mammalian Na+/H+ exchangers of the SLC9A family are widely expressed and involved in numerous essential physiological processes. Their primary function is to mediate 1:1 exchange Na+ for H+ across membrane which they reside, play central roles regulation body, cellular, organellar pH. tightly regulated through mechanisms involving interactions with multiple protein lipid-binding partners, phosphorylations, other posttranslational modifications. Biochemical mutational analyses indicate that SLC9As have a short intracellular N-terminus, 12 transmembrane (TM) helices necessary sufficient ion transport, C-terminal cytoplasmic tail region regulatory roles. No high-resolution structures exist; however, models based on crystal bacterial NhaAs support TM organization suggest TMIV XI may form part ion-translocation pathway, whereas pH sensing involve TMII, TMIX, several loops. Similar most transporters studied, likely exist as coupled dimers membrane, this appears be important well-studied cooperativity binding. The aim work summarize critically discuss currently available evidence structural dynamics, regulation, binding partner SLC9As, focusing particular studied isoform, SLC9A1/NHE1. Further, novel bioinformatic provided some extent challenge existing paradigm how ions transported by mammalian SLC9As.