All cells rely on molecular machines to construct proteins. Among these is the ribosome, a particle found in vast numbers in every cell of all known organisms. The ribosome translates genetic instructions into functional proteins, which then carry out a multitude of tasks, including catalyzing chemical reactions, providing structural support, and transporting substances. A single actively replicating human cell can contain as many as 10 million ribosomes, highlighting the demand for continuous protein production.
The Architectural Blueprint of a Ribosome
Every ribosome is constructed from two primary building blocks: ribosomal RNA (rRNA) and an array of distinct proteins. These components assemble into two separate pieces of unequal size, known as the large and small subunits. These subunits only come together when the process of protein synthesis is ready to begin. A distinction exists between the ribosomes in prokaryotic organisms, like bacteria, and those in eukaryotic organisms, like humans, which is often measured in Svedberg units (S).
Prokaryotic ribosomes are smaller, designated as 70S, and are composed of a 30S small subunit and a 50S large subunit. In contrast, eukaryotic ribosomes are larger and denser, designated as 80S, consisting of a 40S small subunit and a 60S large subunit.
Within the large subunit, there are three distinct pockets that serve as binding sites, known as the A (aminoacyl), P (peptidyl), and E (exit) sites. These sites are fundamental to the ribosome’s ability to process the components required for building a protein. The small subunit possesses a specific site for binding to the genetic blueprint that will be read.
The Process of Protein Synthesis
The ribosome’s primary function is protein synthesis, also called translation. This process converts the genetic information in a messenger RNA (mRNA) molecule into a sequence of amino acids, forming a new protein. The procedure unfolds in three stages: initiation, elongation, and termination.
The process begins with initiation, where the small ribosomal subunit binds to an mRNA molecule and scans it to locate a “start” codon. An initiator transfer RNA (tRNA) molecule, carrying the first amino acid (almost always methionine), then binds to this start codon in the P site. This event triggers the large ribosomal subunit to join the complex, forming a complete ribosome with the A site open for the next step.
Following initiation, the ribosome enters the elongation cycle, where the protein chain is actively built. A new tRNA molecule, carrying the next specified amino acid, enters and binds to the A site. The ribosome then catalyzes the formation of a peptide bond between the new amino acid in the A site and the growing polypeptide chain held by the tRNA in the P site, transferring the chain to the A-site tRNA.
Subsequently, the ribosome moves one codon down the mRNA strand. This translocation shifts the tRNA from the P site to the E site, from which it is released. It also moves the tRNA holding the polypeptide chain from the A site into the P site, leaving the A site vacant for the next incoming tRNA.
This cycle of binding, bond formation, and translocation repeats, with some ribosomes linking 200 amino acids per minute. The process continues until the ribosome encounters a “stop” codon on the mRNA, which signals the termination stage. Release factor proteins recognize the stop codon and bind to the A site.
This binding causes the ribosome to add a water molecule to the end of the polypeptide chain, cleaving the completed protein from the tRNA. The new protein is then released, and the ribosomal subunits, mRNA, and release factors all dissociate, ready to be reused.
Location and Specialization
A ribosome’s location in a eukaryotic cell relates to the final destination of the protein it synthesizes. Ribosomes exist in two populations: free and bound. Both types are structurally identical, and their classification is determined by the protein they are actively producing.
Free ribosomes are found floating throughout the cytosol, the gel-like substance that fills the cell. They produce proteins that will function within the cytosol itself, including enzymes for metabolic pathways or structural proteins for the cytoskeleton. Proteins destined for the nucleus, mitochondria, and chloroplasts are also synthesized on free ribosomes.
Bound ribosomes are attached to the exterior of the endoplasmic reticulum (ER), creating the rough ER. These ribosomes make proteins destined for insertion into membranes, secretion from the cell, or delivery to organelles like the lysosome. Synthesis begins on a free ribosome, but a signal sequence in the new polypeptide chain directs the complex to dock onto the ER membrane, allowing the new protein to be threaded directly into the ER for modification and transport.
Ribosomes in Health and Medicine
Minor defects in ribosome construction or function can lead to human diseases known as ribosomopathies. These disorders arise from mutations in genes that code for ribosomal proteins or rRNA, impairing the cell’s ability to produce proteins correctly. The resulting conditions often affect tissues with high rates of cell division, such as bone marrow.
The structural differences between prokaryotic 70S and eukaryotic 80S ribosomes provide a significant advantage in medicine, forming the basis for how many antibiotics work. These drugs selectively target and inhibit the function of bacterial ribosomes while leaving a patient’s own ribosomes unharmed. This selective toxicity allows for the treatment of bacterial infections without damaging human cells.
For example, tetracycline works by binding to the 30S subunit of bacterial ribosomes, blocking the A site and preventing tRNA molecules from binding. Other antibiotics, such as erythromycin, bind to the 50S subunit and obstruct the exit tunnel where the polypeptide chain emerges. By disrupting the bacterial ribosome’s ability to function, these antibiotics effectively stop the bacteria from growing and multiplying.