Data from: Investigating the Consequences of Protein Stability Disruptions from Copper in Candida albicans [dissertation]

Abstract of associated dissertation:

Copper (Cu) is an essential micronutrient across the evolutionary tree that is used in several biological processes that maintain cellular health. However, Cu has several detrimental effects associated with Cu imbalance including increasing oxidative stress, disrupting protein structures, and compromising crucial biological pathways. Because of the dangers associated with Cu imbalance, evolution has selected for stringent mechanisms to regulate, traffic, and store Cu within the cell. How organisms have evolved Cu regulatory systems depend on the niche that necessitate Cu adaptations.
Candida albicans is an opportunistic fungal pathogen that poses major threats to public health. During periods of infection, the immune system engages in nutritional immunity that includes leveraging Cu as an antimicrobial agent. C. albicans respond to dynamic Cu concentrations by expressing specialized proteins that mitigate Cu stress to promote survival. How cells accommodate Cu in the interim between exposure and the subsequent phenotypic response is not entirely understood. The work here investigates biophysical protein stability changes that inform adaptation in C. albicans to changes in Cu concentrations.
To address how C. albicans are affected by changes in Cu homeostasis, we leverage chemical biology tools to systematically study protein vulnerabilities as a function of Cu disruption. In this work, we use compounds called ionophores that bind Cu to hyperaccumulate Cu in cell to understand the effects of excess Cu. Similarly, we use compounds called chelators that bind Cu to remove Cu that offer an opposite perspective to how cells respond to Cu deprivation. With these Cu binding compounds, we systematically manipulate Cu homeostasis and measure corresponding protein perturbations through mass spectrometry proteomics.
Our results find that Cu-ionophore treatment targets several crucial biological processes including translation, metabolism, and antioxidant regulation. Functional activity assays measure the consequences of Cu-promoted protein stability changes and correlate consistent activity suppression under Cu hyperaccumulation conditions. These global disruptions have important consequences in our understanding of C. albicans adaptations that influence virulence. Altogether, this work contributes to a growing understanding of Cu driving protein stability changes that inform adaptive responses in cells.