Structural basis for translation termination on the 70S ribosome

Area of Science:

• Molecular Biology
• Structural Biology
• Genetics

Background:

• Protein synthesis termination is crucial for cellular function.
• Type I release factors (RF1) mediate termination by recognizing stop codons.
• Understanding RF1-ribosome interactions is key to deciphering translation regulation.

Purpose of the Study:

• To elucidate the structural basis of stop codon recognition by RF1.
• To investigate the mechanism of RF1-mediated peptidyl-tRNA hydrolysis.
• To provide atomic-level insights into translation termination.

Main Methods:

• X-ray crystallography was used to determine the structure of the Thermus thermophilus 70S ribosome complexed with RF1, tRNA, and a UAA stop codon.
• High-resolution (3.2 Å) structural analysis was performed.

Main Results:

• The crystal structure reveals RF1 engaging a UAA stop codon within a specific pocket formed by conserved RF1 elements and 16S ribosomal RNA.
• An induced fit mechanism stabilizes RF1 conformation for interaction with the peptidyl transferase center.
• The conserved GGQ motif's Gln 230 directly participates in peptidyl-tRNA hydrolysis.

Conclusions:

• The structure provides a detailed molecular mechanism for stop codon recognition and translation termination.
• RF1's conserved GGQ motif plays a direct catalytic role in hydrolysis.
• This work enhances our understanding of the intricate process of protein synthesis termination.