TY - JOUR T1 - The structural unit of melanin in the cell wall of the fungal pathogen <em>Cryptococcus neoformans</em> JF - bioRxiv DO - 10.1101/644484 SP - 644484 AU - Emma Camacho AU - Raghav Vij AU - Christine Chrissian AU - Rafael Prados-Rosales AU - David Gil AU - Robert N. O’Meally AU - Radames J.B. Cordero AU - Robert N. Cole AU - J. Michael McCaffery AU - Ruth E. Stark AU - Arturo Casadevall Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/05/20/644484.abstract N2 - Melanins are synthesized macromolecules that are found in all biological kingdoms. These pigments have a myriad of roles that range from microbial virulence to key components of the innate immune response in invertebrates. Melanins also exhibit unique properties with potential applications in physics and material sciences, ranging from electrical batteries to novel therapeutics. In the fungi, melanins such as eumelanins, are components of the cell wall that provide protection against biotic and abiotic elements. Elucidation of the smallest fungal cell wall-asociated melanin unit that serves as a building block is critical to understand the architecture of these polymers, its interaction with surrounding components, and their functional versatility. In this study, we used isopycnic gradient sedimentation, NMR, EPR, high-resolution microscopy, and proteomics to analyze the melanin in the cell wall of the human pathogenic fungus Cryptococcus neoformans. We observed that melanin is assembled into the cryptococcal cell wall in spherical structures of ∼200 nm in diameter, termed melanin granules, which are in turn composed of nanospheres of ∼30 nm in diameter, the fungal melanosomes. We noted that melanin granules are closely associated with proteins that may play critical roles in the fungal melanogenesis and the supramolecular structure of this polymer. Using this structural information, we propose a model for C. neoformans melanization that is similar to the process used in animal melanization and is consistent with the phylogenetic relatedness of the fungal and animal kingdoms. ER -