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PMID: 21617092 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 108 ·No. 24 ·2011-06-14 ·Pages 9827-32

Adamczyk AJ, Warshel A

Abstract

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.

MeSH Terms
Allosteric Regulation Binding Sites/genetics Catalytic Domain Enzyme Activation GTP Phosphohydrolases/chemistry,genetics,metabolism Guanosine Triphosphate/chemistry,metabolism Hydrolysis Models, Molecular Molecular Structure Mutation Peptide Elongation Factor Tu/chemistry,metabolism Protein Structure, Tertiary Ribosomes/chemistry,metabolism Static Electricity Thermodynamics
Chemicals
Guanosine Triphosphate GTP Phosphohydrolases Peptide Elongation Factor Tu
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Adamczyk Andrew J
Department of Chemistry, 418 Seeley G Mudd Building, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089-1062, USA.
Warshel Arieh
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1105714108
Published
2011-06-14
Epub
2011-00-26
Pages
9827-32
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC3116401
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.1105714108 PMC Full Text View journal details
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