Digestomics: elucidating protein catabolism through the quantitative mapping of in vivo, endogenous peptides to the proteome at an amino acid level of resolution.
Date
2020-03-13
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Abstract
Plasmodium falciparum is the most lethal malaria-causing parasite. During the human stage of its lifecycle it invades erythrocytes and rapidly degrades 65-70% of the cytoplasmic hemoglobin. Despite extensive in vitro investigation of the proteases responsible for this impressive catabolic activity, the definitive purpose of this digestion remains unresolved. Many of the known proteases have been knocked out yet these parasites have minimal growth phenotypes. The common explanation is that proteolytic redundancy allows parasites to survive. I, however, hypothesize that the protease(s) essential for hemoglobin catabolism have yet to be identified. To test this, I developed a new approach to directly investigate in vivo protein catabolism. I analyze a panel of knockout parasites and show that in vivo proteolytic cleavage patterns are unchanged in knockouts, find evidence that published cut sites match poorly to in vivo data and find convincing proteolytic patterns suggesting the presence of previously unidentified cut sites.
Description
Keywords
Plasmodium falciparum, Proteolysis, Digestomics, Mass Spectrometry
Citation
Bingeman, T. S. (2020). Digestomics: elucidating protein catabolism through the quantitative mapping of in vivo, endogenous peptides to the proteome at an amino acid level of resolution. (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.