Tuning of the Na,K-ATPase by the beta subunit.

ABSTRACT: The vital gradients of Na(+) and K(+) across the plasma membrane of animal cells are maintained by the Na,K-ATPase, an ?? enzyme complex, whose ? subunit carries out the ion transport and ATP hydrolysis. The specific roles of the ? subunit isoforms are less clear, though ?2 is essential for motor physiology in mammals. Here, we show that compared to ?1 and ?3, ?2 stabilizes the Na(+)-occluded E1P state relative to the outward-open E2P state, and that the effect is mediated by its transmembrane domain. Molecular dynamics simulations further demonstrate that the tilt angle of the ? transmembrane helix correlates with its functional effect, suggesting that the relative orientation of ? modulates ion binding at the ? subunit. ?2 is primarily expressed in granule neurons and glomeruli in the cerebellum, and we propose that its unique functional characteristics are important to respond appropriately to the cerebellar Na(+) and K(+) gradients.

SUBMITTER: Hilbers F 

PROVIDER: S-EPMC4742777 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature