During translation in molecular biology, what is the correct pathway followed by an aminoacyl–tRNA as it progresses through the ribosome during polypeptide elongation (identify the order of ribosomal sites)?

Introduction:
Ribosomes translate the genetic code in mRNA into a polypeptide by cycling transfer RNAs (tRNAs) through three functional sites. Mastering the order of these sites is essential to understand elongation, proofreading, and the energy flow that drives protein synthesis. This question asks for the correct tRNA pathway on the ribosome during elongation: the aminoacyl (A), peptidyl (P), and exit (E) sites.

Given Data / Assumptions:

• Elongation involves repetitive decoding, peptide bond formation, and translocation.
• tRNAs carry amino acids as aminoacyl–tRNA, or hold the nascent chain as peptidyl–tRNA.
• Sites are arranged on the ribosome as A (acceptor), P (peptidyl), and E (exit).

Concept / Approach:
Aminoacyl–tRNA enters the A site when its anticodon matches the mRNA codon (with help from elongation factors). Peptidyl transferase activity (in the large subunit rRNA) transfers the growing chain from the P-site tRNA to the amino acid in the A site. After peptide bond formation, EF-G (in bacteria) or eEF2 (in eukaryotes) uses GTP to translocate the ribosome so that the A-site peptidyl–tRNA moves to the P site and the deacylated tRNA in P moves to E for exit. Thus, the directional flow is A → P → E.

Step-by-Step Solution:

Verification / Alternative check:
Antibiotics like chloramphenicol (blocks peptidyl transferase) and tetracycline (blocks A-site entry) confirm the functional order. Toeprinting and cryo-EM structures show tRNA occupancy consistent with A → P → E cycling.

Why Other Options Are Wrong:

• P → entry → exit or A → P → entry: there is no formal “entry site”; the standard nomenclature is A, P, E.
• P → A → E: peptide bond formation requires aminoacyl–tRNA in A first, not initial occupancy of P by the incoming tRNA.
• E → A → P: reverse order; E is the exit only.

Common Pitfalls:
Confusing mRNA movement with tRNA site changes, and thinking the A site is for “already peptidyl” tRNA rather than the incoming aminoacyl–tRNA.

Final Answer:
A site → P site → E site