The 80S ribosome is a complex and highly dynamic molecular machine found in the cells of all eukaryotes, including animals, plants, fungi, and protists. It serves as the primary factory for a process called translation, converting the genetic code carried by messenger RNA (mRNA) into functional polypeptide chains, the building blocks of proteins. This cellular component synthesizes the thousands of different proteins required for a cell’s structure, function, and signaling. The structure and function of the 80S ribosome are tailored to the eukaryotic cellular environment, allowing for the precise and regulated production of diverse proteins.
Defining the 80S Structure
The designation 80S refers to the ribosome’s sedimentation coefficient, measured in Svedberg units (S). This unit reflects the rate at which the particle settles in a centrifugal field, influenced by its size, shape, and density, which is why the subunits’ S values do not arithmetically add up to 80. The complete 80S ribosome is composed of two unequal parts: a smaller 40S subunit and a larger 60S subunit.
The small 40S subunit binds the mRNA template and monitors the fidelity of the genetic code during translation. It is constructed from one 18S ribosomal RNA (rRNA) molecule and approximately 33 associated ribosomal proteins. The large 60S subunit is the site where the chemical reaction of protein synthesis occurs, creating the peptide bonds that link amino acids together.
This larger subunit is composed of three different rRNA molecules (5S, 5.8S, and 28S rRNAs) and around 49 different ribosomal proteins. Ribosomes are found either freely floating in the cytoplasm or attached to the membranes of the rough endoplasmic reticulum (RER). Free ribosomes synthesize proteins for internal use, while RER-bound ribosomes produce proteins intended for secretion or integration into cellular membranes.
The Mechanism of Protein Synthesis
The fundamental job of the 80S ribosome is to execute translation, which involves reading the sequence of codons on an mRNA molecule and linking corresponding amino acids into a polypeptide chain. This coordinated process is divided into three major stages: initiation, elongation, and termination. The ribosome possesses three binding sites positioned at the interface between the two subunits: the A (aminoacyl), P (peptidyl), and E (exit) sites.
Initiation
Translation begins with initiation, where the small 40S subunit first recognizes and binds to the mRNA molecule, typically near the Kozak sequence in eukaryotes. An initiator transfer RNA (tRNA), carrying the first amino acid (methionine), then binds directly to the P site of the 40S subunit, recognizing the start codon (AUG) on the mRNA. The large 60S subunit subsequently joins the complex to form the complete, functional 80S ribosome, which is poised to begin protein synthesis.
Elongation
Elongation is a cycle of events that rapidly extends the polypeptide chain. A new tRNA molecule, carrying the next amino acid specified by the mRNA, enters the A site. The 60S subunit then catalyzes peptidyl transfer, forming a peptide bond that connects the amino acid in the A site to the growing polypeptide chain held by the tRNA in the P site.
Following peptide bond formation, the ribosome undergoes translocation, shifting exactly three nucleotides along the mRNA strand. This movement causes the tRNAs to shift sequentially: the now-empty tRNA moves from the P site to the E site, and the tRNA holding the polypeptide chain moves from the A site to the P site. The empty tRNA is released from the E site, and the newly vacant A site is ready to receive the next charged tRNA, allowing the cycle to repeat until the entire mRNA message is read.
Termination
Termination occurs when a stop codon (UAA, UAG, or UGA) enters the A site. Since no tRNA molecule recognizes these stop codons, a protein known as a release factor binds to the A site instead. The binding of the release factor triggers the hydrolysis of the bond between the polypeptide and the tRNA in the P site, releasing the completed protein chain. The 80S ribosome then dissociates back into its 40S and 60S subunits, which can be recycled to initiate translation on another mRNA molecule.
How 80S Ribosomes Differ from 70S Ribosomes
The 80S ribosome is structurally distinct from the 70S ribosome, a smaller type found in prokaryotic organisms like bacteria and archaea. The eukaryotic 80S ribosome is significantly larger and more intricate, typically exceeding 3.3 million Daltons in molecular mass, compared to the 70S ribosome’s mass of about 2.5 million Daltons and containing fewer proteins and a smaller total amount of rRNA.
The subunit composition is a defining distinction: the 80S is made of 40S and 60S subunits, while the 70S ribosome is built from 30S and 50S subunits. Eukaryotic ribosomes also contain a higher protein-to-RNA ratio and feature many more accessory proteins. The 70S ribosome is also found inside eukaryotic organelles like mitochondria and chloroplasts, a reflection of their ancient bacterial origins.
This structural difference has practical implications for medicine and antibiotic development. Many effective antibiotics are designed to specifically target the unique structure of the bacterial 70S ribosome. Because the human 80S ribosome is structurally different, these drugs can selectively inhibit protein synthesis in invading bacterial cells without damaging the host’s own ribosomes. This structural divergence is the cornerstone of selective toxicity.