Cell surface functions for iron acquisition in C.albicans and C. neoformans.

The diagrams on the left show the polysaccharides and iron-related uptake functions at the fungal cell surface. For C. albicans, the iron-uptake proteins include the ferritin-binding protein Als3, ferric reductases (Fre1/10), a multicopper oxidase (Fet3), and an iron permease (Ftr1) [8]–[10]. The components of a heme uptake pathway include the receptor Rbt5 and some of the proteins involved in internalization [18], [19]. These proteins are depicted schematically as contributing to endocytosis of heme and/or hemoglobin. For C. neoformans, surface polysaccharides are shown for the capsule (GXM, GXMGal) and the cell wall, and iron-uptake functions include putative ferric reductase activity (Fre), a multicopper oxidase (Cfo1), and an iron permease (Cft1) [7], [37]. The role of Cig1 and known or hypothesized functions for endocytosis are also shown in a schematic depiction [27], [30]. The diagrams on the right present the structures of Als3 [10], Rbt5 [17]–[19], and Cig1 ([27]; B. Cadieux, unpublished) to depict shared and distinct domains. Note that the polypeptides are not draw to scale and the actual amino acid length of each is indicated. Molecular modeling suggests that the immunoglobulin-like fold of Als3 may interact with cadherins [10]. However, the structural features that contribute to iron acquisition have not been defined for any of the proteins.