Accurate estimation of translation rate parameters explains stoichiometric protein synthesis in E. coli

E. coli has long served as a prominent model organism for exploring the fundamental principles of cellular and molecular genetics. Nevertheless, there remain unresolved questions surrounding the origins of certain experimental observations related to the regulation of gene expression in E. coli. One notable example is the production of multiprotein complexes where the synthesis of their essential subunits is proportional to their stoichiometry in the complex. In this study, we employ a combination of next-generation sequencing data and stochastic simulations of protein synthesis to elucidate the underlying mechanisms governing the proportional synthesis of proteins within these multicomponent complexes. Our findings reveal that the initiation rates for translating all subunits in these complexes are directly proportional to their stoichiometry, thereby establishing a constraint on protein synthesis kinetics that achieves proportionality without necessitating feedback mechanisms. Additionally, our research identifies that translation initiation rates in E. coli are impacted by factors such as coding sequence length and the prevalence of A and C nucleotides near the start codon. Consequently, this investigation rationalizes the significance of conserved and nonrandom gene features in dictating translation kinetics, unveiling a pivotal principle in the regulation of protein synthesis.