Solid-state NMR reveals the carbon-based molecular architecture of Cryptococcus neoformans fungal eumelanins in the cell wall

Subhasish Chatterjee, Rafael Prados-Rosales, Boris Itin, Arturo Casadevall, Ruth E. Stark

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Melanin pigments protect against both ionizing radiation and free radicals and have potential soil remediation capabilities. Eumelanins produced by pathogenic Cryptococcus neoformans fungi are virulence factors that render the fungal cells resistant to host defenses and certain antifungal drugs. Because of their insoluble and amorphous characteristics, neither the pigment bonding framework nor the cellular interactions underlying melanization of C. neoformans have yielded to comprehensive molecular-scale investigation. This study used the C. neoformans requirement of exogenous obligatory catecholamine precursors for melanization to produce isotopically enriched pigment "ghosts" and applied 2D <sup>13</sup>C-<sup>13</sup>C correlation solid-state NMR to reveal the carbon-based architecture of intact natural eumelanin assemblies in fungal cells. We demonstrated that the aliphatic moieties of solid C. neoformans melanin ghosts include cell-wall components derived from polysaccharides and/or chitin that are associated proximally with lipid membrane constituents. Prior to development of the mature aromatic fungal pigment, these aliphatic moieties form a chemically resistant framework that could serve as the scaffold for melanin synthesis. The indole-based core aromatic moieties show interconnections that are consistent with proposed melanin structures consisting of stacked planar assemblies, which are associated spatially with the aliphatic scaffold. The pyrrole aromatic carbons of the pigments bind covalently to the aliphatic framework via glycoside or glyceride functional groups. These findings establish that the structure of the pigment assembly changes with time and provide the first biophysical information on the mechanism by which melanin is assembled in the fungal cell wall, offering vital insights that can advance the design of bioinspired conductive nanomaterials and novel therapeutics.

Original languageEnglish (US)
Pages (from-to)13779-13790
Number of pages12
JournalJournal of Biological Chemistry
Volume290
Issue number22
DOIs
StatePublished - May 29 2015

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Cryptococcus neoformans
Melanins
Pigments
Cell Wall
Carbon
Cells
Nuclear magnetic resonance
Scaffolds
Glycerides
Pyrroles
Chitin
Nanostructures
Virulence Factors
Cellular Structures
Membrane Lipids
Glycosides
Ionizing Radiation
Ionizing radiation
Free Radicals
Catecholamines

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Solid-state NMR reveals the carbon-based molecular architecture of Cryptococcus neoformans fungal eumelanins in the cell wall. / Chatterjee, Subhasish; Prados-Rosales, Rafael; Itin, Boris; Casadevall, Arturo; Stark, Ruth E.

In: Journal of Biological Chemistry, Vol. 290, No. 22, 29.05.2015, p. 13779-13790.

Research output: Contribution to journalArticle

Chatterjee, Subhasish ; Prados-Rosales, Rafael ; Itin, Boris ; Casadevall, Arturo ; Stark, Ruth E. / Solid-state NMR reveals the carbon-based molecular architecture of Cryptococcus neoformans fungal eumelanins in the cell wall. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 22. pp. 13779-13790.
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