Structure, mechanism and lipid-mediated remodeling of the mammalian Na⁺/H⁺ exchanger NHA2.

ABSTRACT: The Na⁺/H⁺ exchanger SLC9B2, also known as NHA2, correlates with the long-sought-after Na⁺/Li⁺ exchanger linked to the pathogenesis of diabetes mellitus and essential hypertension in humans. Despite the functional importance of NHA2, structural information and the molecular basis for its ion-exchange mechanism have been lacking. Here we report the cryo-EM structures of bison NHA2 in detergent and in nanodiscs, at 3.0 and 3.5 Å resolution, respectively. The bison NHA2 structure, together with solid-state membrane-based electrophysiology, establishes the molecular basis for electroneutral ion exchange. NHA2 consists of 14 transmembrane (TM) segments, rather than the 13 TMs previously observed in mammalian Na⁺/H⁺ exchangers (NH

SUBMITTER: Matsuoka R 

PROVIDER: S-EPMC8850199 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature