Elongation and Peptide Bond Formation

Elongation is the repetitive phase of translation in which the ribosome reads the messenger RNA one codon at a time, adding amino acids to a growing polypeptide. Each cycle couples accurate selection of an aminoacyl-transfer RNA, formation of a peptide bond, and movement of the ribosome to the next codon.

Definition

Elongation is the iterative ribosomal cycle of codon-directed aminoacyl-tRNA selection, peptide bond formation between the P-site peptidyl-tRNA and the A-site aminoacyl-tRNA, and GTP-driven translocation that advances the ribosome by one codon.

Scope

This topic covers the three coupled events of the elongation cycle: decoding and delivery of aminoacyl-tRNA by elongation factor Tu (or eEF1A), catalysis of the peptide bond at the ribosome's peptidyl transferase centre, and translocation driven by elongation factor G (or eEF2). It also addresses how speed and accuracy are balanced. It is a mechanistic topic, not clinical guidance.

Core questions

• How is the correct aminoacyl-tRNA selected for each codon?
• How does the ribosome catalyse peptide bond formation?
• What drives translocation along the messenger RNA?
• How are elongation speed and fidelity balanced?

Key concepts

• Aminoacyl (A), peptidyl (P), and exit (E) sites
• Elongation factor Tu / eEF1A
• Peptidyl transferase centre
• Elongation factor G / eEF2 and translocation
• GTP hydrolysis
• Decoding fidelity and proofreading

Key theories

Ribosomal peptidyl transfer as RNA catalysis

The peptidyl transferase centre is composed of ribosomal RNA, indicating that the ribosome is fundamentally a ribozyme that promotes peptide bond formation largely by substrate positioning.

Induced-fit decoding and kinetic proofreading

Cognate codon-anticodon pairing triggers conformational changes that accelerate GTP hydrolysis on elongation factor Tu, while a proofreading step after hydrolysis gives a second opportunity to reject incorrect tRNAs, jointly enhancing accuracy.

Mechanisms

In each elongation cycle, elongation factor Tu (eEF1A in eukaryotes) delivers an aminoacyl-tRNA to the ribosomal A site as a complex with GTP; correct codon-anticodon pairing is sensed in the decoding centre and stimulates GTP hydrolysis, after which a proofreading step can still reject near-cognate tRNAs. The accepted aminoacyl-tRNA is accommodated into the peptidyl transferase centre, where ribosomal RNA catalyses transfer of the growing chain onto the new amino acid, forming a peptide bond. Elongation factor G (eEF2) then uses GTP hydrolysis to drive translocation, moving the tRNAs and mRNA so that the next codon enters the A site and the deacylated tRNA exits. Structural snapshots have visualised these states, clarifying how decoding, catalysis, and movement are coordinated.

Clinical relevance

Several antibiotics and toxins act on elongation, for example by blocking aminoacyl-tRNA delivery, the peptidyl transferase reaction, or translocation, which makes this phase important for understanding antimicrobial action and certain toxins. This entry explains molecular mechanisms and is not a basis for individual diagnostic or treatment decisions.

Evidence & guidelines

The elongation mechanism is supported by kinetic, biochemical, and high-resolution structural studies of bacterial and eukaryotic ribosomes, consolidated in major review literature.

History

Biochemical work in the 1960s and 1970s identified the elongation factors and the basic A, P, and E site framework. Kinetic studies in the 1990s established how GTP hydrolysis powers decoding and translocation, and crystallographic and cryo-EM structures from the 2000s onward captured the ribosome in successive elongation states, confirming RNA catalysis at the peptidyl transferase centre.

Key figures

• V. Ramakrishnan
• Marina Rodnina
• Wolfgang Wintermeyer
• Rachel Green

Seminal works

• schmeing-2009
• voorhees-2009
• rodnina-1997

Frequently asked questions

Does protein catalyse the peptide bond?

No; structural studies show the peptidyl transferase centre is made of ribosomal RNA, so the ribosome forms peptide bonds as a ribozyme, largely by positioning the reacting substrates.

What makes the ribosome move along the messenger RNA?

Translocation is driven by elongation factor G (eEF2 in eukaryotes) using the energy of GTP hydrolysis to advance the ribosome by exactly one codon each cycle.