U01.01.017 Protein synthesis

Protein synthesis, the transformation of genetic instructions into functional proteins, is a fundamental process in living cells. Here’s a breakdown for Step 1 of the USMLE:

The Stages of Protein Synthesis:

1. Initiation: Setting the Stage (Requires GTP)

Eukaryotic Initiation Factors (eIFs) Play Matchmaker:
- These protein helpers identify the 5′ cap on the mRNA, a crucial recognition point.
- They then assist in assembling the 40S ribosomal subunit with the initiator tRNA (carrying methionine in eukaryotes).
Putting it All Together: Once the mRNA and the 60S ribosomal subunit join the complex, the eIFs are released. This step also requires GTP for energy.

Key Point: In eukaryotes, the assembled ribosome consists of a 40S and a 60S subunit, forming the 80S ribosome. Prokaryotes have a smaller 70S ribosome (30S + 50S subunits).

2. Elongation: Building the Chain (Requires GTP and ATP)

“Going APE”: Remember this acronym to understand the key sites on the ribosome:
- A site (Aminoacyl site): Here, the incoming aminoacyl-tRNA (tRNA carrying an amino acid) binds to the mRNA codon. (Except for the initiator methionine, which binds to the P site). This step involves an elongation factor and GTP.
- P site (Peptidyl site): This site accommodates the growing peptide chain.
- E site (Exit site): This site holds the empty tRNA as it prepares to exit the ribosome.
The “Ribozyme” Steps Up: The ribosomal RNA (rRNA) acts as a catalyst (ribozyme) for peptide bond formation. It transfers the growing polypeptide chain to the amino acid on the tRNA in the A site.
Moving on Down the Line: The ribosome “walks” three nucleotides towards the 3′ end of the mRNA. This movement, called translocation, shifts the peptidyl-tRNA to the P site and positions the empty tRNA for exit from the E site. Translocation also requires GTP for energy.

3. Termination: Wrapping Up (Requires GTP)

Release Factors Recognize the Stop Sign: Eukaryotic release factors (eRFs) identify the stop codon (UAA, UAG, or UGA) on the mRNA. This signals the end of protein synthesis.
Protein Released, Ribosome Recycled: The completed polypeptide chain is released from the ribosome. The ribosomal subunits dissociate and can be used for another round of protein synthesis. This process also requires GTP.

Key Takeaways for Step 1:

Protein synthesis involves three main stages: initiation, elongation, and termination.
GTP is required for initiation and translocation during elongation.
ATP is used for activating amino acids (charging tRNAs).
Understanding the roles of ribosomes, tRNAs, and protein factors is essential for protein synthesis.
Remembering “going APE” can help you recall the key functional sites on the ribosome.

USMLE Step 1 Review Series

Curriculum

U01.01.017 Protein synthesis

The Stages of Protein Synthesis:

Key Takeaways for Step 1:

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