Service interruption on Monday 11 July from 12:30 to 13:00: all the sites of the CCSD (HAL, Epiciences, SciencesConf, AureHAL) will be inaccessible (network hardware connection).
Skip to Main content Skip to Navigation
Journal articles

Mechanism of activation of elongation factor Tu by ribosome: Catalytic histidine activates GTP by protonation.

Abstract : Elongation factor Tu (EF-Tu) is central to prokaryotic protein synthesis as it has the role of delivering amino-acylated tRNAs to the ribosome. Release of EF-Tu, after correct binding of the EF-Tu:aa-tRNA complex to the ribosome, is initiated by GTP hydrolysis. This reaction, whose mechanism is uncertain, is catalyzed by EF-Tu, but requires activation by the ribosome. There have been a number of mechanistic proposals, including those spurred by a recent X-ray crystallographic analysis of a ribosome:EF-Tu:aa-tRNA:GTP-analog complex. In this work, we have investigated these and alternative hypotheses, using high-level quantum chemical/molecular mechanical simulations for the wild-type protein and its His85Gln mutant. For both proteins, we find previously unsuggested mechanisms as being preferred, in which residue 85, either His or Gln, directly assists in the reaction. Analysis shows that the RNA has a minor catalytic effect in the wild-type reaction, but plays a significant role in the mutant by greatly stabilizing the reaction's transition state. Given the similarity between EF-Tu and other members of the translational G-protein family, it is likely that these mechanisms of ribosome-activated GTP hydrolysis are pertinent to all of these proteins.
Document type :
Journal articles
Complete list of metadata
Contributor : Denis Roura Connect in order to contact the contributor
Submitted on : Friday, September 27, 2013 - 2:09:53 PM
Last modification on : Saturday, June 25, 2022 - 8:27:21 PM

Links full text




Alexey Aleksandrov, Martin J Field. Mechanism of activation of elongation factor Tu by ribosome: Catalytic histidine activates GTP by protonation.. RNA, Cold Spring Harbor Laboratory Press, 2013, 19 (9), pp.1218-25. ⟨10.1261/rna.040097.113⟩. ⟨hal-00866971⟩



Record views