Cell surface functions for iron acquisition in <i>C.</i><i>albicans</i> and <i>C. neoformans</i>.

<p>The diagrams on the left show the polysaccharides and iron-related uptake functions at the fungal cell surface. For <i>C. albicans</i>, the iron-uptake proteins include the ferritin-binding protein Als3, ferric reductases (Fre1/10), a multicopper oxidase (Fet3), and an iron permease (Ftr1) <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003498#ppat.1003498-Almeida1" target="_blank">[8]</a>–<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003498#ppat.1003498-Liu1" target="_blank">[10]</a>. The components of a heme uptake pathway include the receptor Rbt5 and some of the proteins involved in internalization <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003498#ppat.1003498-Weissman2" target="_blank">[18]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003498#ppat.1003498-Braun1" target="_blank">[19]</a>. These proteins are depicted schematically as contributing to endocytosis of heme and/or hemoglobin. For <i>C. neoformans</i>, 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) <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003498#ppat.1003498-Jung1" target="_blank">[7]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003498#ppat.1003498-Kumar1" target="_blank">[37]</a>. The role of Cig1 and known or hypothesized functions for endocytosis are also shown in a schematic depiction <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003498#ppat.1003498-Cadieux1" target="_blank">[27]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003498#ppat.1003498-Hu1" target="_blank">[30]</a>. The diagrams on the right present the structures of Als3 <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003498#ppat.1003498-Liu1" target="_blank">[10]</a>, Rbt5 <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003498#ppat.1003498-Weissman1" target="_blank">[17]</a>–<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003498#ppat.1003498-Braun1" target="_blank">[19]</a>, and Cig1 (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003498#ppat.1003498-Cadieux1" target="_blank">[27]</a>; 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 <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003498#ppat.1003498-Liu1" target="_blank">[10]</a>. However, the structural features that contribute to iron acquisition have not been defined for any of the proteins.</p>