A novel proton transfer mechanism in the SLC11 family of divalent metal ion transporters.

ABSTRACT: In humans, the H⁺-coupled Fe²⁺ transporter DMT1 (SLC11A2) is essential for proper maintenance of iron homeostasis. While X-ray diffraction has recently unveiled the structure of the bacterial homologue ScaDMT as a LeuT-fold transporter, the exact mechanism of H⁺-cotransport has remained elusive. Here, we used a combination of molecular dynamics simulations, in silico pK _a calculations and site-directed mutagenesis, followed by rigorous functional analysis, to discover two previously uncharacterized functionally relevant residues in hDMT1 that contribute to H⁺-coupling. E193 plays a central role in proton binding, thereby affecting transport properties and electrogenicity, while N472 likely coordinates the metal ion, securing an optimal

SUBMITTER: Pujol-Gimenez J 

PROVIDER: S-EPMC5533754 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature