During the elongation phase of translation, a charged tRNA enters the A site of the ribosome. What is the immediate next step catalyzed by the ribosome?

Core Concept

PILLAR 1 — MOLECULAR/CONCEPTUAL MECHANISM

Step-by-Step Analysis

The ribosome functions as a ribozyme—a catalytic complex composed of ribosomal RNA (rRNA) and structural proteins—orchestrating polypeptide synthesis through precise molecular geometry. During elongation, the ribosome contains three tRNA-binding sites arranged directionally: the aminoacyl (A) site, the peptidyl (P) site, and the exit (E) site. When a charged aminoacyl-tRNA, escorted by elongation factor Tu (EF-Tu) complexed with GTP, achieves correct codon-anticodon base pairing within the A site, conformational changes propagate through the 16S rRNA of the 30S subunit. This structural rearrangement triggers GTP hydrolysis by EF-Tu, causing EF-Tu to dissociate and allowing the aminoacyl-tRNA to fully accommodate into the A site. The immediate next catalytic event is peptidyl transfer: the ribosome's peptidyl transferase center (PTC), located in the 23S rRNA of the 50S subunit, catalyzes a nucleophilic attack. The α-amino group (–NH₂) of the amino acid attached to the A-site tRNA attacks the carbonyl carbon of the ester bond linking the growing polypeptide chain to the 3'-OH of the terminal adenosine (A76) of the P-site tRNA. This transesterification reaction transfers the entire nascent polypeptide from the P-site tRNA to the A-site tRNA, forming a new peptide bond. Notably, the ribosome stabilizes the reaction transition state through precise positioning of substrates within the PTC—no enzymatic side chains directly participate; rather, rRNA folding creates an electrostatic environment that accelerates peptide bond formation by approximately 10⁷-fold relative to the uncatalyzed reaction.

Why Other Options Are Wrong

PILLAR 2 — STEP-BY-STEP LOGIC

The question specifically asks for the immediate next step after a charged tRNA enters and accommodates within the A site. Having established the molecular choreography above, the sequence is unambiguous: accommodation is followed directly by peptidyl transfer. The growing polypeptide chain, esterified to the P-site tRNA, is transferred to the amino acid on the A-site tRNA via peptide bond formation. Only after this covalent transfer does translocation occur—driven by elongation factor G (EF-G) and GTP hydrolysis—which advances the ribosome three nucleotides (one codon) along the mRNA in the 5'→3' direction. Translocation simultaneously shifts the now-deacylated P-site tRNA to the E site (where it dissociates) and moves the peptidyl-tRNA from the A site to the P site, clearing the A site for the next charged tRNA. Therefore, peptide bond formation precedes and is mechanistically prerequisite for translocation, not the reverse. The correct answer (B) identifies peptide bond formation as this immediate post-accommodation catalytic event.

PILLAR 3 — DISTRACTOR ANALYSIS

Option A (translocation of the ribosome along mRNA) entraps students who conflate the chronological order of elongation substeps. Translocation absolutely occurs during each elongation cycle, but it follows peptide bond formation, requiring EF-G-mediated movement after the polypeptide has been transferred to the A-site tRNA. Selecting this option reflects a sequencing error—failing to recognize that the ribosome must first forge the new covalent bond before mechanical advancement.

Option C (release of the polypeptide from the ribosome) describes a termination event mediated by release factors (RF1 or RF2 in prokaryotes), not an elongation step. When a stop codon (UAA, UAG, or UGA) occupies the A site, a release factor binds and triggers hydrolysis of the ester bond between the polypeptide and the P-site tRNA. Students selecting this option confuse elongation with termination, two mechanistically and temporally distinct phases.

Option D (binding of initiator tRNA to the start codon) describes the initiation phase, wherein formylmethionyl-tRNAᵢᴹᵉᵗ pairs with the AUG start codon in the P site, facilitated by initiation factors (IF1, IF2, IF3). This event precedes elongation entirely and is incompatible with a scenario where the A site already contains an incoming charged tRNA during active chain extension.

Option E (hydrolysis of the aminoacyl-tRNA bond before peptide bond formation) represents a misunderstanding of substrate utilization. The ester bond between a tRNA and its cognate amino acid is not hydrolyzed prior to peptidyl transfer; rather, the amino group of the A-site amino acid attacks the P-site ester linkage directly. Premature hydrolysis would release the incoming amino acid as a free molecule, rendering it useless for incorporation—an energetically wasteful process the cell avoids through tight ribosomal regulation.