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Release factors eRF1 and RF2: a universal mechanism controls the large conformational changes
1Basic Research Program, SAIC-Frederick, Inc., Laboratory of Experimental and Computational Biology, NCI-Frederick, National Institutes of Health, Frederick, MD 21702, USA. mab@ncifcrf.gov
The Journal of Biological Chemistry
|October 12, 2004
Summary
Class I release factors (RF1 and RF2) undergo conformational changes, acting as molecular machines fueled by histidine protonation to terminate protein synthesis across species.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Class I release factors (RF1 and RF2) are crucial for terminating protein synthesis.
- Their crystal structures do not fit the ribosomal binding pocket, suggesting conformational flexibility.
- Cryoelectron microscopy indicates significant conformational changes upon ribosome binding.
Purpose of the Study:
- To investigate the conformational dynamics of eRF1 and RF2.
- To elucidate the mechanisms controlling their transitions between free and ribosome-bound states.
- To understand how these factors function as molecular machines in protein synthesis termination.
Main Methods:
- Molecular dynamics simulations
- Structural alignment
- Electrostatic analysis of domain interactions
Main Results:
- Relaxed eRF1 conformation resembles ribosome-bound RF2 observed via cryo-EM.
- Conformational transitions are likely controlled by histidine protonation.
- Specific motif distances change significantly, favoring different conformations based on environmental factors.
Conclusions:
- RF1 and RF2 function as molecular machines, likely powered by histidine protonation.
- Conformational control mechanisms are conserved, suggesting similar protein synthesis termination processes across species.
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