Stochastic Ordering of Complexoform Protein Assembly by Genetic Circuits

Top-down proteomics has enabled the elucidation of heterogeneous protein complexes with different cofactors, post-translational modifications, and membership. This heterogeneity is believed to play a previously unknown role in cellular processes. The molecular forms complex have come be called “complex isoform” or “complexoform”. Despite complexoform, it remains unclear how whether circuits control distribution complexoform. To help address this issue, we first simulate generic three-protein complexoform reveal its by timing gene transcription, mRNA translation, transport. Based on experiments, show that genes arranged single operon, cascade, as two operons all give rise composition because differences protein-synthesis order. We also changes kinetics expression, transport, binding dramatically alter Furthermore, both stochastic transient assembly when expression occur concurrently. test our model against biological cellulosome system. With biologically relevant rates, find genetic circuitry controls average final variation structure. Our results highlight importance circuit architecture determining