Visualization of codon-dependent conformational rearrangements during translation termination

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Ribosome-mediated translation termination relies on class 1 release factors (RFs).
• The precise molecular mechanisms governing the high-fidelity recognition of stop codons by RFs remain incompletely understood.
• Understanding these mechanisms is crucial for comprehending the accuracy of protein synthesis.

Purpose of the Study:

• To elucidate the structural basis for the high-fidelity recognition of stop codons by class 1 release factors (RFs).
• To compare the conformational states of cognate and near-cognate ribosome termination complexes.

Main Methods:

• Utilized Fe(II)-derivatized release factors (RFs) for structural probing experiments.
• Analyzed structural differences in ribosome termination complexes.

Main Results:

• Identified distinct structural differences between cognate and near-cognate ribosome termination complexes.
• Documented close interactions between RFs and the small-subunit decoding center.
• Observed increased interactions involving the RF switch loop and subunit interface regions.
• Determined the precise orientation of RFs within the large subunit for optimal catalytic activity.

Conclusions:

• The study provides an unprecedented structural view of how authentic stop-codon recognition is signaled to the ribosome.
• These events involve a cascade of interactions from the small to the large ribosomal subunit.
• The findings explain how RFs achieve precise orientation for efficient peptidyl transferase center activity, ensuring translation fidelity.