title: Nutritional immunity: homology modeling of Nramp metal import.
abstract: The Natural resistance-associated macrophage proteins (Nramp1 and 2) are proton-dependent solute carriers of divalent metals such as Fe(2+) and Mn(2+) (Slc11a1 and 2). Their expression in both resting and microbicidal macrophages which metabolize iron differently, raises questions about Nramp mechanism of Me(2+) transport and its impact in distinct phenotypic contexts. We developed a low resolution 3D model for Slc11 based on detailed phylogeny and remote homology threading using Escherichia coli Nramp homolog (proton-dependent Mn(2+) transporter, MntH) as experimental system. The predicted fold is consistent with determinations of transmembrane topology and activity; it indicates Slc11 carriers are part of the LeuT superfamily. Homology implies that inverted structural symmetry facilitates Slc11 H(+)-driven Me(2+) import and provides a 3D framework to test structure-activity relationships in macrophages and study functional evolution of MntH/Nramp (Slc11) carriers.
authors.affiliation: INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, 531, Bd des prairies, H7V 1B7, Laval, QC, Canada. mathieu.cellier@iaf.inrs.ca
authors.forename: Mathieu F M
authors.initials: MF
authors.lastname: Cellier
mesh_terms: D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D008670:Metals / Q000378:metabolism*; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D008670:Metals; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2