A conserved histidine in switch-II of EF-G moderates release of inorganic phosphate
10.1038/srep12970
Crossref journal-article
Springer Science and Business Media LLC
Scientific Reports (297)
Abstract

AbstractElongation factor G (EF-G), a translational GTPase responsible for tRNA-mRNA translocation possesses a conserved histidine (H91 in Escherichia coli) at the apex of switch-II, which has been implicated in GTPase activation and GTP hydrolysis. While H91A, H91R and H91E mutants showed different degrees of defect in ribosome associated GTP hydrolysis, H91Q behaved like the WT. However, all these mutants, including H91Q, are much more defective in inorganic phosphate (Pi) release, thereby suggesting that H91 facilitates Pi release. In crystal structures of the ribosome bound EF-G•GTP a tight coupling between H91 and the γ-phosphate of GTP can be seen. Following GTP hydrolysis, H91 flips ~140° in the opposite direction, probably with Pi still coupled to it. This, we suggest, promotes Pi to detach from GDP and reach the inter-domain space of EF-G, which constitutes an exit path for the Pi. Molecular dynamics simulations are consistent with this hypothesis and demonstrate a vital role of an Mg2+ ion in the process.

Bibliography

Koripella, R. K., Holm, M., Dourado, D., Mandava, C. S., Flores, S., & Sanyal, S. (2015). A conserved histidine in switch-II of EF-G moderates release of inorganic phosphate. Scientific Reports, 5(1).

Authors 6
  1. Ravi Kiran Koripella (first)
  2. Mikael Holm (additional)
  3. Daniel Dourado (additional)
  4. Chandra Sekhar Mandava (additional)
  5. Samuel Flores (additional)
  6. Suparna Sanyal (additional)
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Dates
Type When
Created 10 years ago (Aug. 12, 2015, 5:32 a.m.)
Deposited 2 years, 7 months ago (Jan. 5, 2023, 6:49 p.m.)
Indexed 2 months ago (June 26, 2025, 1:46 p.m.)
Issued 10 years ago (Aug. 12, 2015)
Published 10 years ago (Aug. 12, 2015)
Published Online 10 years ago (Aug. 12, 2015)
Funders 0

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@article{Koripella_2015, title={A conserved histidine in switch-II of EF-G moderates release of inorganic phosphate}, volume={5}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/srep12970}, DOI={10.1038/srep12970}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Koripella, Ravi Kiran and Holm, Mikael and Dourado, Daniel and Mandava, Chandra Sekhar and Flores, Samuel and Sanyal, Suparna}, year={2015}, month=aug }