Converting structural information into an allosteric-energy-based picture for elongation factor Tu activation by the ribosome

The crucial process of aminoacyl-tRNA delivery to the ribosome is energized by the GTPase reaction of the elongation factor Tu (EF-Tu). Advances in the elucidation of the structure of the EF-Tu/ribosome complex provide the rare opportunity of gaining a detailed understanding of the activation proces...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-06, Vol.108 (24), p.9827-9832
Main Authors: Adamczyk, Andrew J, Warshel, Arieh
Format: Article
Language:English
Subjects:
Allosteric properties
Allosteric Regulation
Binding Sites - genetics
Biochemistry
Biological Sciences
Catalysis
Catalytic Domain
Coordinate systems
Electrostatics
Enzyme Activation
Free energy
GTP Phosphohydrolases - chemistry
GTP Phosphohydrolases - genetics
GTP Phosphohydrolases - metabolism
Guanosine Triphosphate - chemistry
Guanosine Triphosphate - metabolism
guanosinetriphosphatase
Hydrolysis
Lead
Models, Molecular
Molecular Structure
mutants
Mutation
Peptide Elongation Factor Tu - chemistry
Peptide Elongation Factor Tu - metabolism
Peptide elongation factors
Phosphates
Protein Structure, Tertiary
Proteins
Ribosomes
Ribosomes - chemistry
Ribosomes - metabolism
Signal transduction
Simulation
Static Electricity
Thermodynamics
Transfer RNA
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Summary:The crucial process of aminoacyl-tRNA delivery to the ribosome is energized by the GTPase reaction of the elongation factor Tu (EF-Tu). Advances in the elucidation of the structure of the EF-Tu/ribosome complex provide the rare opportunity of gaining a detailed understanding of the activation process of this system. Here, we use quantitative simulation approaches and reproduce the energetics of the GTPase reaction of EF-Tu with and without the ribosome and with several key mutants. Our study provides a novel insight into the activation process. It is found that the critical H84 residue is not likely to behave as a general base but rather contributes to an allosteric effect, which includes a major transition state stabilization by the electrostatic effect of the P loop and other regions of the protein. Our findings have general relevance to GTPase activation, including the processes that control signal transduction.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1105714108