Cryo-EM structure of the human NKCC1 transporter reveals mechanisms of ion coupling and specificity.

ABSTRACT: The sodium-potassium-chloride transporter NKCC1 of the SLC12 family performs Na⁺ -dependent Cl^- - and K⁺ -ion uptake across plasma membranes. NKCC1 is important for regulating cell volume, hearing, blood pressure, and regulation of hyperpolarizing GABAergic and glycinergic signaling in the central nervous system. Here, we present a 2.6 Å resolution cryo-electron microscopy structure of human NKCC1 in the substrate-loaded (Na⁺ , K⁺ , and 2 Cl^- ) and occluded, inward-facing state that has also been observed for the SLC6-type transporters MhsT and LeuT. Cl^- binding at the Cl1 site together with the nearby K⁺ ion provides a crucial bridge between the LeuT-fold scaffold and bundle domains. Cl^- -io

SUBMITTER: Neumann C 

PROVIDER: S-EPMC9713717 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature