Mechanism of the electroneutral sodium/proton antiporter PaNhaP from transition-path shooting.

ABSTRACT: Na⁺/H⁺ antiporters exchange sodium ions and protons on opposite sides of lipid membranes. The electroneutral Na⁺/H⁺ antiporter NhaP from archaea Pyrococcus abyssi (PaNhaP) is a functional homolog of the human Na⁺/H⁺ exchanger NHE1, which is an important drug target. Here we resolve the Na⁺ and H⁺ transport cycle of PaNhaP by transition-path sampling. The resulting molecular dynamics trajectories of repeated ion transport events proceed without bias force, and overcome the enormous time-scale gap between seconds-scale ion exchange and microseconds simulations. The simulations reveal a hydrophobic gate to the extracellular side that opens and closes in response to the transporter domain motion. Weakening

SUBMITTER: Okazaki KI 

PROVIDER: S-EPMC6465308 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature