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The ribosome termination complex remodels release factor RF3 and ejects GDP
Li Li1,2, Mariia Yu Rybak3, Jinzhong Lin4,5
1State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Nature Structural & Molecular Biology
|July 19, 2024
Summary
The 70S ribosome termination complex (70S-TC) acts as a guanine nucleotide exchange factor, facilitating GDP release from release factor 3 (RF3). This ribosome remodeling mechanism ensures efficient recycling of release factors during translation termination.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Translation termination relies on release factors (RF1, RF2) and the GTPase RF3 for recycling.
- RF3 must exchange GDP for GTP after dissociating from the ribosome to re-enter the cycle.
- The 70S ribosome termination complex (70S-TC) is known to accelerate this GDP/GTP exchange for RF3.
Purpose of the Study:
- To elucidate the mechanism of GDP dissociation from RF3 catalyzed by the Escherichia coli 70S-TC.
- To understand the structural basis of RF3 recycling during translation termination.
Main Methods:
- Cryogenic-electron microscopy (cryo-EM) was used to determine high-resolution structures.
- Structural analysis of the 70S-TC bound to RF1 and RF3.
Main Results:
- The non-rotated ribosome bound to RF1 remodels RF3, inducing a peptide flip that ejects GDP.
- GTP binding enables RF3 to dock at the GTPase center, promoting RF1 dissociation.
- The 70S-TC allosterically dismantles the phosphate-binding groove in RF3, facilitating GDP release.
Conclusions:
- The 70S-TC functions as a guanine nucleotide exchange factor for RF3.
- Structural insights reveal a novel ribosome-mediated mechanism for RF3 GDP/GTP exchange.
- This study uncovers a previously unrecognized allosteric function of the ribosome in regulating release factor recycling.
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