Potential Effect of Post-Transcriptional Substitutions of Tyrosine for Cysteine Residues on Transformation of Amyloidogenic Proteins

Abstract

The review considers the reasons and consequences of post-transcriptional tyrosine substitutions for cysteine residues. Main attention is paid to the Tyr/Cys substitutions that arise during gene expression in bacterial systems at the stage of protein translation as a result of misrecognition of the similar mRNA codons. Notably, translation errors generally occur relatively rarely - from 10^-4 to 10^-3 errors per codon for E. coli cells, but in some cases the error rate increases significantly. For example, this is typical for certain pairs of codons, when the culture conditions change or in the presence of antibiotics. Thus, with overproduction of the recombinant human alpha-synuclein in E. coli cells, the content of the mutant form with the replacement of Tyr136 (UAC codon) with a cysteine residue (UGC codon) can reach 50%. Possible reasons for the increased production of alpha-synuclein with the Tyr136Cys substitution are considered, as well as consequences of the presence of mutant forms in preparations of amyloidogenic proteins when studying their pathological transformation in vitro. A separate section is devoted to the Tyr/Cys substitutions occurring due to mRNA editing by adenosine deaminases, which is typical for eukaryotic organisms, and the possible role of this process in the amyloid transformation of proteins associated with neurodegenerative diseases.

Keywords: Tyr/Cys substitutions; amyloidogenesis; amyloidogenic proteins; protein production in bacteria; synuclein; translation errors.