The Mechanism for Activation of GTP Hydrolysis on the Ribosome
-
1.
MRC Laboratory of Molecular Biology
Abstract
Protein synthesis requires several guanosine triphosphatase (GTPase) factors, including elongation factor Tu (EF-Tu), which delivers aminoacyl–transfer RNAs (tRNAs) to the ribosome. To understand how the ribosome triggers GTP hydrolysis in translational GTPases, we have determined the crystal structure of EF-Tu and aminoacyl-tRNA bound to the ribosome with a GTP analog, to 3.2 angstrom resolution. EF-Tu is in its active conformation, the switch I loop is ordered, and the catalytic histidine is coordinating the nucleophilic water in position for inline attack on the γ-phosphate of GTP. This activated conformation is due to a critical and conserved interaction of the histidine with A2662 of the sarcin-ricin loop of the 23S ribosomal RNA. The structure suggests a universal mechanism for GTPase activation and hydrolysis in translational GTPases on the ribosome.
Additional Information
© 2010 American Association for the Advancement of Science. 29 June 2010; accepted 3 September 2010. We thank R. Green for reagents and D. de Sanctis at the European Synchrotron Radiation Facility for facilitating data collection. This work was supported by the Medical Research Council UK, the Wellcome Trust, the Agouron Institute, and the Louis-Jeantet Foundation. R.M.V. is supported by a Gates-Cambridge scholarship, and T.M.S. by the Human Frontier Science Program and Emmanuel College. V.R. is on the Scientific Advisory Board and holds stock options in Rib-X pharmaceuticals. Transfer of Thermus thermophilis ribosome strain T.th. HB8-MRC-MSAW1 requires a Materials Transfer Agreement with the MRC. Coordinates and structure factors have been deposited at the Protein Data Bank with accession codes 2xqd and 2xqe.Attached Files
Accepted Version - emss-54562.pdf
Supplemental Material - Voorhees.SOM.pdf
Files
emss-54562.pdf
Additional details
Identifiers
- PMCID
- PMC3763471
- Eprint ID
- 84352
- DOI
- 10.1126/science.1194460
- Resolver ID
- CaltechAUTHORS:20180117-074150683
Related works
- Describes
- 10.1126/science.1194460 (DOI)
Funding
- Medical Research Council (UK)
- Wellcome Trust
- Agouron Institute
- Louis-Jeantet Foundation
- Gates-Cambridge Scholarship
- Human Frontier Science Program
- Emmanuel College
Dates
- Created
-
2018-01-17Created from EPrint's datestamp field
- Updated
-
2023-02-28Created from EPrint's last_modified field