Ribosome Structure and Function

The ribosome is the large ribonucleoprotein machine that carries out translation, reading messenger RNA and synthesising proteins. Built from ribosomal RNA and many proteins arranged in two subunits, it both decodes codons and catalyses peptide bond formation.

Definition

The ribosome is a two-subunit ribonucleoprotein complex whose small subunit decodes messenger RNA codons and whose large subunit catalyses peptide bond formation through its ribosomal RNA, making the ribosome a ribozyme.

Scope

This topic covers the two-subunit architecture of the ribosome, its ribosomal RNA and protein composition, the decoding centre on the small subunit and the peptidyl transferase centre on the large subunit, the A, P, and E transfer RNA sites, and the finding that catalysis is performed by RNA. It is a structural and mechanistic topic, not clinical guidance.

Core questions

• What are the components and overall architecture of the ribosome?
• Where do decoding and peptide bond formation occur?
• Why is the ribosome considered a ribozyme?
• How do bacterial and eukaryotic ribosomes differ?

Key concepts

• Small and large ribosomal subunits
• Ribosomal RNA (rRNA) and ribosomal proteins
• Decoding centre (small subunit)
• Peptidyl transferase centre (large subunit)
• A, P, and E transfer RNA sites
• Polysomes
• Antibiotic binding sites

Key theories

The ribosome is a ribozyme

Atomic structures of the large subunit showed no protein side chains at the catalytic site, indicating that ribosomal RNA forms the peptidyl transferase centre and catalyses peptide bond formation.

Mechanisms

The ribosome consists of a small subunit, which binds messenger RNA and monitors codon-anticodon pairing in its decoding centre, and a large subunit, which holds the peptidyl transferase centre and a tunnel through which the nascent chain exits. Transfer RNAs occupy three sites, the aminoacyl (A), peptidyl (P), and exit (E) sites, spanning both subunits, and move through them as the ribosome elongates and translocates. High-resolution structures of bacterial subunits and complete ribosomes, and later of the eukaryotic ribosome, revealed that ribosomal RNA forms both the decoding and catalytic centres, establishing the ribosome as an RNA-based machine; many of these structures also mapped where antibiotics bind. Multiple ribosomes can translate one messenger RNA simultaneously, forming polysomes.

Clinical relevance

Because numerous clinically important antibiotics bind to and inhibit bacterial ribosomes, and because defects in ribosome biogenesis cause a group of disorders known as ribosomopathies, ribosome structure is central to antimicrobial pharmacology and certain diseases. This entry explains structure and function and is not a basis for individual diagnostic or treatment decisions.

Evidence & guidelines

The structural picture summarised here rests on X-ray crystallographic and cryo-electron-microscopy studies of bacterial and eukaryotic ribosomes, consolidated in major review literature.

History

Ribosomes were identified as the sites of protein synthesis in the mid-twentieth century, but their detailed architecture emerged only around 2000, when crystal structures of the large and small bacterial subunits, and then of the complete 70S ribosome with mRNA and tRNA, were solved. The eukaryotic ribosome was resolved at high resolution in 2011, and advances in cryo-electron microscopy have since captured the ribosome in many functional states.

Key figures

• Thomas Steitz
• V. Ramakrishnan
• Ada Yonath
• Marat Yusupov
• Joachim Frank

Seminal works

• nissen-2000
• carter-2000
• selmer-2006
• ben-shem-2011

Frequently asked questions

What is the ribosome made of?

The ribosome is built from ribosomal RNA and many ribosomal proteins organised into two subunits; the RNA forms both the decoding centre and the catalytic peptidyl transferase centre.

Why do many antibiotics target the ribosome?

Bacterial ribosomes differ enough from human ribosomes that drugs can bind functional sites on the bacterial ribosome and block protein synthesis selectively, which is why the ribosome is a major antibiotic target.