Locking Two Rigid-body Bundles in an Outward-Facing Conformation: The Ion-coupling Mechanism in a LeuT-fold Transporter.

ABSTRACT: Secondary active transporters use electrochemical gradient of ions to fuel the "uphill" translocation of the substrate following the alternating-access model. The coupling of ions to conformational dynamics of the protein remains one of the least characterized aspects of the transporter function. We employ extended molecular dynamics (MD) simulations to examine the Na⁺-binding effects on the structure and dynamics of a LeuT-fold, Na⁺-coupled secondary transporter (Mhp1) in its major conformational states, i.e., the outward-facing (OF) and inward-facing (IF) states, as well as on the OF ↔ IF state transition. Microsecond-long, unbiased MD simulations illustrate that Na⁺ stabilizes an OF conformation favorable for substrate association, by binding to a highly

SUBMITTER: Li J 

PROVIDER: S-EPMC6925253 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature