NRAMP DEFINES A FAMILY OF MEMBRANE-PROTEINS

Nramp (natural resistance-associated macrophage protein) is a newly id entified family of integral membrane proteins whose biochemical functi on is unknown. We report on the identification of Nramp homologs from the fly Drosophila melanogaster, the plant Oryza sativa, and the yeast Saccharomyces cerevisiae. Optimal alignment of protein sequences requ ired insertion of very few gaps and revealed remarkable sequence ident ity of 28% (yeast), 40% (plant), and 55% (fly) with the mammalian prot eins (46%, 58%, and 73% similarity), as well as a common predicted tra nsmembrane topology. This family is defined by a highly conserved hydr ophobic core encoding 10 transmembrane segments. Other features of thi s hydrophobic core include several invariant charged residues, helical periodicity of sequence conservation suggesting conserved and noncons erved faces for several transmembrane helices, a consensus transport s ignature on the intracytoplasmic face of the membrane, and structural determinants previously described in ion channels. These characteristi cs suggest that the Nramp polypeptides form part of a group of transpo rters or channels that act on as yet unidentified substrates.