Structural basis for translation termination by archaeal RF1 and GTP-bound EF1α complex

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Translation termination is crucial for protein synthesis, involving class I and II release factors (RFs).
• In eukaryotes and archaea, these RFs form a heterodimeric complex and function GTP-dependently.
• The structural mechanism of this complex during translation termination remains largely unknown.

Purpose of the Study:

• To elucidate the structural mechanism of translation termination by the archaeal class I and II RF complex.
• To understand how archaeal elongation factor 1 alpha (aEF1α) functions as a class II RF in complex with archaeal RF1 (aRF1).

Main Methods:

• Determined the crystal structure of the archaeal RF1-aEF1α (aRF1·aEF1α) complex.
• Analyzed the structural resemblance to the tRNA·EF-Tu complex.
• Investigated the mechanism coupling GTP hydrolysis and stop codon recognition.

Main Results:

• Reported the first crystal structure of an active class I and II RF complex (aRF1·aEF1α).
• The complex structure mimics the tRNA·EF-Tu complex, suggesting tRNA mimicry for delivery to the ribosomal A site.
• Provided insights into the coupling of GTP hydrolysis by aEF1α to stop codon recognition and peptidyl-tRNA hydrolysis by aRF1.

Conclusions:

• The structure of the aRF1·aEF1α complex provides a mechanistic basis for translation termination in archaea.
• tRNA mimicry is a key strategy for efficient delivery of release factors to the ribosome.
• The study sheds light on the molecular evolution and diverse functions of aEF1α.