Protein Synthesis Mechanisms in Mycobacterial Systems

Protein synthesis in mycobacteria encompasses a coordinated sequence of events from transcription initiation to ribosomal translation and polypeptide folding. Transcription by RNA polymerase yields messenger RNA that is processed and bound by ribosomal subunits to form the 70S ribosome. Initiation factors govern start codon recognition, followed by elongation mediated by aminoacyl-tRNAs and elongation factors that ensure correct codon–anticodon pairing and translocation along the mRNA. The peptidyl transferase centre within the large ribosomal subunit catalyses peptide bond formation. Mycobacteria possess unique ribosomal proteins and rRNA expansion segments that confer adaptations in polysome organisation and translation kinetics. Under stress conditions such as zinc limitation or hypoxia, alternative ribosomal proteins or dormancy-associated factors can stabilise ribosomes and modulate translational capacity. Aminoacyl-tRNA synthetases charge tRNAs with cognate amino acids, while auxiliary GTPases and chaperones assist in ribosomal assembly and nascent chain folding. This intricate machinery is a prime target for antibiotics and a focus for developing new antimycobacterial agents.

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Technical terms

70S ribosome: The bacterial ribosome composed of a 30S small subunit and a 50S large subunit, responsible for mRNA decoding and peptide bond formation.

tRNA: Transfer RNA, an adaptor molecule that delivers specific amino acids to the ribosome in accordance with mRNA codons.

Aminoacyl-tRNA synthetase: An enzyme that esterifies a specific amino acid to its corresponding tRNA, ensuring translational fidelity.

Elongation factor: A GTP-binding protein that facilitates the delivery of aminoacyl-tRNAs to the ribosome and promotes translocation during peptide elongation.

Operon: A cluster of co-transcribed genes under the control of a single promoter, often encoding functionally related proteins such as alternative ribosomal subunits.

Peptidyl transferase centre: The catalytic site located in the large ribosomal subunit that mediates peptide bond formation between adjacent amino acids.

References

1. The Complete Structure of the Mycobacterium smegmatis 70S Ribosome. Cell Reports (2017).
2. The Dormancy Regulator DosR Controls Ribosome Stability in Hypoxic Mycobacteria*. Journal of Biological Chemistry (2012).
3. Alternative ribosomal proteins are required for growth and morphogenesis of Mycobacterium smegmatis under zinc limiting conditions. PLOS ONE (2018).
4. Structural Diversity in Bacterial Ribosomes: Mycobacterial 70S Ribosome Structure Reveals Novel Features. PLOS ONE (2012).
5. Reconstitution of Protein Translation of Mycobacterium Reveals Functional Conservation and Divergence with the Gram-Negative Bacterium Escherichia coli. PLOS ONE (2016).