Nramp: from sequence to structure and mechanism of divalent metal import.

摘要: Abstract Mn and Fe are important for energy metabolism oxidative stress resistance cells maintain adequate stores survival prevention of toxicity. Membrane permeases the natural resistance-associated macrophage protein (Nramp) family importing protons divalent metals conserved from bacteria to man. Nramp hydrophobic core relates structurally a superfamily cation-driven carriers with inverted symmetry. Molecular phylogeny sequence features support pseudo-symmetric three-dimensional (3D) model, remote ancestry LeuT superfamily. Genetic analyses suggest conservation marks transition phylogenetic out-group may relate metal selectivity. Three phylogroups bacterial proton-dependent manganese transporters (MntH) demonstrate specific patterns suggesting functional constraints linked ecological or taxonomical distributions, which contribute virulence. 3D model is supported experimentally by transmembrane topology structure–function studies Escherichia coli mouse homologs as well peptide structure analyses. Eukaryotic Nramps required homeostasis, contributing in multicellular organisms subcellular systemic traffic intercellular signaling. subjected elaborate regulation including developmental control gene expression, targeting, dynamic metallo-dependent messenger RNA stability trafficking. Several human pathologies result defects Nramp-dependent 2+ transport, iron overload, neurodegenerative diseases innate susceptibility infectious diseases.