Unraveling the structural elements of pH sensitivity and substrate binding in the human zinc transporter SLC39A2 (ZIP2).

ABSTRACT: The transport and ion-coupling mechanisms of ZIP transporters remain largely uncharacterized. Previous work in our laboratory has revealed that the solute carrier family 39 member A2 (SLC39A2/ZIP2) increases its substrate transport rate in the presence of extracellular H⁺ Here, we used a combination of in silico and in vitro techniques involving structural modeling, mutagenesis, and functional characterization in HEK293 cells to identify amino acid residues potentially relevant for both the ZIP2-H⁺ interaction and substrate binding. Our ZIP2 models revealed a cluster of charged residues close to the substrate-translocation pore. Interestingly, the H63A substitution completely abrogated pH sensitivity, and substitutions of Glu-67 and Phe-269 altered the p

SUBMITTER: Gyimesi G 

PROVIDER: S-EPMC6527156 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature