ribosome uses cooperative conformational changes to maximize and regulate the efficiency of translation

One of the most challenging unanswered questions regarding the structural biology of biomolecular machines such as the two-subunit ribosome is whether and how these machines coordinate seemingly independent and random conformational fluctuations to maximize and regulate their functional efficiencies...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2014-08, Vol.111 (33), p.12073-12078
Main Authors: Ning, Wei, Fei, Jingyi, Gonzalez, Ruben L.
Format: Article
Language:English
Subjects:
Allosteric regulation
Antibiotics
Biological Sciences
Biophysics
Catalysis
Enzymes
Fluorescence Resonance Energy Transfer
Gene expression regulation
Kinetics
Molecular physics
Mutagenesis
Nucleic Acid Conformation
Protein Biosynthesis
Ribonucleic acid
Ribosomes
Ribosomes - metabolism
RNA
RNA, Transfer - chemistry
Rotation
Rotational dynamics
Static Electricity
Transfer RNA
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Summary:One of the most challenging unanswered questions regarding the structural biology of biomolecular machines such as the two-subunit ribosome is whether and how these machines coordinate seemingly independent and random conformational fluctuations to maximize and regulate their functional efficiencies. To address this question, we have used ribosome mutagenesis or a ribosome-targeting antibiotic to predictably perturb the dynamics of intersubunit rotation, a structural rearrangement of the ribosome that is essential for the translocation and ejection of ribosome-bound tRNAs during translation. Concomitantly, we have used single-molecule fluorescence resonance energy transfer (smFRET) to characterize the effects of these perturbations on the dynamics of ribosomal L1 stalk movements and ribosome-bound tRNA reconfigurations, conformational changes that are likewise essential for the translocation and ejection of tRNAs during translation. Together with the results of complementary biochemical studies, our smFRET studies demonstrate that the ribosome uses cooperative conformational changes to maximize and regulate the efficiency with which it translocates and ejects tRNAs during translation. We propose that the ribosome employs cooperative conformational changes to efficiently populate global conformational states that are productive for translation, that translation factors exploit this cooperativity as part of their mechanisms of action, and that antibiotics exploit it to maximize the potency with which they inhibit translation. It is likely that similar cooperative conformational changes underlie the function and regulation of other biomolecular machines.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1401864111