Computational Analysis of Human Cysteine Redox Proteoforms Reveals Novel Insights

Abstract

Since cysteine redox proteoforms (i) are virtually unstudied, we derived novel insights by computationally analysing the human proteome. Our analysis revealed a vast, effectively infinite, theoretical i space housing 3.02 x 10e169 unique cysteine redox proteoforms. For over 80% and 99% of the human proteome, the i space comprises 6.83 x 10e8 and 1.76 x 10e31 unique proteoforms, respectively. The heterogenous distribution of the i space by gene ontology terms, suggests, but does not prove, functional speciation. To theoretically limit the number of cysteine redox proteoforms that can be downloaded from the abstract i cloud, we implement novel equations. Protein copy numbers limit the i space by 161-logs to 4.04 x 10e7 unique cysteine redox proteoforms per HeLa cell. An immutable law: the number of cysteine redox proteoform molecules (Ni) must equal the number of cysteine-containing protein molecules. We compute an Ni value of 1.70 x 10e9 per HeLa cell. While Ni will be displaced from thermodynamic equilibrium towards the reduced state (e.g., 90%-reduced), it is possible that the number of partially oxidised cysteine redox proteoform molecules is in the order of 10e6-8 per HeLa cell. Consistent with this, 100%-oxidised forms were observed in 60% of the proteins studied to date. Our analysis advances understanding of redox biology at the proteoform level.