Stochastic ordering of complexoform protein assembly by genetic circuits

Jensen, Mikkel Herholdt and Morris, Eliza J. and Hai , Tran and Nash, Michael A. and Tan, Cheemeng. (2020) Stochastic ordering of complexoform protein assembly by genetic circuits. PLoS Computational Biology, 16 (6). e1007997.

PDF - Published Version
Available under License CC BY (Attribution).


Official URL: https://edoc.unibas.ch/80294/

Downloads: Statistics Overview


Top-down proteomics has enabled the elucidation of heterogeneous protein complexes with different cofactors, post-translational modifications, and protein membership. This heterogeneity is believed to play a previously unknown role in cellular processes. The different molecular forms of a protein complex have come to be called "complex isoform" or "complexoform". Despite the elucidation of the complexoform, it remains unclear how and whether cellular circuits control the distribution of a complexoform. To help address this issue, we first simulate a generic three-protein complexoform to reveal the control of its distribution by the timing of gene transcription, mRNA translation, and protein transport. Overall, we ran 265 computational experiments: each averaged over 1,000 stochastic simulations. Based on the experiments, we show that genes arranged in a single operon, a cascade, or as two operons all give rise to the different protein composition of complexoform because of timing differences in protein-synthesis order. We also show that changes in the kinetics of expression, protein transport, or protein binding dramatically alter the distribution of the complexoform. Furthermore, both stochastic and transient kinetics control the assembly of the complexoform when the expression and assembly occur concurrently. We test our model against the biological cellulosome system. With biologically relevant rates, we find that the genetic circuitry controls the average final complexoform assembly and the variation in the assembly structure. Our results highlight the importance of both the genetic circuit architecture and kinetics in determining the distribution of a complexoform. Our work has a broad impact on our understanding of non-equilibrium processes in both living and synthetic biological systems.
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Synthetic Systems (Nash)
UniBasel Contributors:Nash, Michael
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Library of Science
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
edoc DOI:
Last Modified:16 Mar 2021 11:35
Deposited On:16 Mar 2021 11:35

Repository Staff Only: item control page