Ribosome

Ribosomes are fundamental molecular machines found in all living cells, responsible for translating messenger RNA into polypeptide chains during protein synthesis. As ribonucleoprotein complexes, they consist of ribosomal RNA and numerous associated proteins organised into two unequal subunits. Despite structural variations between bacteria, archaea and eukaryotes, ribosomes share a conserved core architecture that reflects their ancient evolutionary origin.
The ribosome plays a central role in gene expression. It reads mRNA codons sequentially and recruits transfer RNA molecules carrying specific amino acids to form a growing polypeptide chain. Once synthesised, the chain undergoes folding to achieve its functional three-dimensional structure. Multiple ribosomes may translate a single mRNA simultaneously, forming a polysome.

Overview of Protein Synthesis

Protein synthesis proceeds through the coordinated phases of initiation, elongation, termination and recycling. The start codon, AUG, is universally recognised as signalling the beginning of translation. During elongation, each mRNA codon is matched with a complementary anticodon on a tRNA molecule, ensuring the correct amino acid is incorporated. Termination occurs when the ribosome encounters one of three stop codons—UAA, UAG or UGA—and no corresponding tRNA binds. The two ribosomal subunits then dissociate and may be reused for subsequent translation cycles.
Amino acids are brought to the ribosome as aminoacylated tRNAs. Each tRNA contains an anticodon loop that pairs with the appropriate codon on the mRNA, ensuring fidelity. The ribosome catalyses peptide bond formation, a function carried out by ribosomal RNA rather than protein. Consequently, the ribosome is classified as a ribozyme.

Structural Organisation

Ribosomes contain a small and a large subunit that join during translation. Each subunit comprises rRNA molecules and a set of proteins in stoichiometric association. The small subunit decodes the mRNA, while the large subunit contains the catalytic peptidyl transferase centre.
In all organisms, ribosomes are measured in Svedberg units, which relate to their sedimentation rate in centrifugation. Because this measure is not directly additive, the combined Svedberg value of the two subunits is lower than their sum.
Prokaryotic ribosomesBacterial ribosomes are 70S particles composed of a 30S small subunit and a 50S large subunit. The 30S subunit contains a 16S rRNA and about 21 proteins, while the 50S subunit contains 5S and 23S rRNAs together with around 31 proteins. Structural analyses show that proteins are largely peripheral, acting as scaffolds that stabilise rRNA, with the catalytic activity residing in the RNA.
Archaeal ribosomesArchaeal ribosomes resemble bacterial ones in size and overall sedimentation characteristics (70S), but their protein composition is more similar to that of eukaryotes. Additional archaeal ribosomal proteins have eukaryotic homologues, further highlighting evolutionary connections.
Eukaryotic ribosomesEukaryotic cytosolic ribosomes are larger 80S particles comprising a 40S small subunit and a 60S large subunit. The 40S subunit contains an 18S rRNA and about 33 proteins. The 60S subunit contains 5S, 5.8S and 28S rRNAs and roughly 49 proteins. These distinctions make ribosomes valuable targets in pharmacology, as antibiotics can selectively inhibit bacterial translation without disrupting eukaryotic ribosomes.

Ribosomes in Organelles

Ribosomes also exist within mitochondria and plastids. These organelle ribosomes are more similar to bacterial ribosomes and reflect their endosymbiotic origins. Mitochondrial ribosomes, or mitoribosomes, differ markedly from bacterial ribosomes in rRNA length and protein composition. Many mitochondrial rRNAs are shortened, particularly in animals and fungi, where the 5S rRNA may be absent and functionally replaced by other structural components. In contrast, plant mitoribosomes contain extended rRNAs and unique proteins such as pentatricopeptide repeat proteins.
Chloroplast ribosomes, or plastoribosomes, are generally closer to bacterial ribosomes in structure. Certain algal groups with nucleomorphs—vestigial nuclei retained from secondary endosymbiosis—may house eukaryotic-type 80S ribosomes in these compartments.

Functional Sites and Catalysis

Within the ribosome, tRNAs interact at distinct binding sites. The A (aminoacyl), P (peptidyl) and E (exit) sites coordinate tRNA positioning during translation. Affinity-labelling experiments have mapped several ribosomal proteins near these functional centres. The peptidyl transferase reaction is performed by rRNA, establishing the ribosome as an RNA-based catalyst.
Translational fidelity is supported by specific interactions between the 3′ end of 16S rRNA and proteins such as S1 and S21 in bacteria, which participate in translation initiation. Structural studies also show that proteins near the decoding or catalytic centres do not directly mediate chemical reactions but provide structural support that optimises rRNA conformation.

Discovery and Structural Elucidation

Ribosomes were first observed in the 1950s using electron microscopy by George Emil Palade, who identified them as dense granular structures within cells. They were subsequently termed “ribosomes” to reflect their ribonucleic acid content. Foundational work in characterising and understanding ribosome structure earned Palade, Albert Claude and Christian de Duve the Nobel Prize in Physiology or Medicine in 1974.
Later breakthroughs in X-ray crystallography and cryo-electron microscopy enabled detailed resolution of ribosomal structures. These achievements culminated in the 2009 Nobel Prize in Chemistry awarded to Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath for elucidating the molecular mechanisms of translation.

Antimicrobial and Biomedical Relevance

Differences between bacterial and eukaryotic ribosomes underpin the mechanism of many antibiotics. Several antibacterial agents bind selectively to sites on bacterial rRNA, disrupting initiation, elongation or termination processes. Because eukaryotic ribosomes differ in sequence and structure, such treatments interfere minimally with human translation. This selectivity makes the ribosome an important target in antimicrobial therapy.