Limits...
Molecular dynamics of ribosomal elongation factors G and Tu.

Kulczycka K, Długosz M, Trylska J - Eur. Biophys. J. (2010)

Bottom Line: We observed enhanced mobility of EF-G domains III, IV, and V and of tRNA in the EF-Tu:tRNA complex.EF-Tu:GDP complex acquired a configuration different from that found in the crystal structure of EF-Tu with a GTP analogue, showing conformational changes in the switch I and II regions.The calculated electrostatic properties of elongation factors showed no global similarity even though matching electrostatic surface patches were found around the domain I that contacts the ribosome, and in the GDP/GTP binding region.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, Pawinskiego 5A, 02-106 Warsaw, Poland.

ABSTRACT
Translation on the ribosome is controlled by external factors. During polypeptide lengthening, elongation factors EF-Tu and EF-G consecutively interact with the bacterial ribosome. EF-Tu binds and delivers an aminoacyl-tRNA to the ribosomal A site and EF-G helps translocate the tRNAs between their binding sites after the peptide bond is formed. These processes occur at the expense of GTP. EF-Tu:tRNA and EF-G are of similar shape, share a common binding site, and undergo large conformational changes on interaction with the ribosome. To characterize the internal motion of these two elongation factors, we used 25 ns long all-atom molecular dynamics simulations. We observed enhanced mobility of EF-G domains III, IV, and V and of tRNA in the EF-Tu:tRNA complex. EF-Tu:GDP complex acquired a configuration different from that found in the crystal structure of EF-Tu with a GTP analogue, showing conformational changes in the switch I and II regions. The calculated electrostatic properties of elongation factors showed no global similarity even though matching electrostatic surface patches were found around the domain I that contacts the ribosome, and in the GDP/GTP binding region.

Show MeSH
Average structures of the three most numerous populations of EF-G (left) and EF-Tu:tRNA (right) derived on the basis of clustering of their RMSD matrices presented in Fig. 3
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3045518&req=5

Fig4: Average structures of the three most numerous populations of EF-G (left) and EF-Tu:tRNA (right) derived on the basis of clustering of their RMSD matrices presented in Fig. 3

Mentions: To discern the conformational movements in EF-G and EF-Tu:tRNA, we quantified the changes in RMSD between each trajectory frame. The RMSD-matrices and the cluster analysis are presented in Fig. 3. We observed several clusters with a time-span between 1.5 and 6 ns; 16 groups of different configurations for EF-G (Fig. 3), 22 groups for EF-G:GDP (data not shown), and 11 groups for EF-Tu:tRNA (Fig. 3). The average structures of the most numerous populations of EF-G and EF-Tu:tRNA are shown in Fig. 4. The average RMSD between the structures within each cluster is about 1 Å. The RMSD between structures from different clusters ranges from 2 to 3 Å. In both cases the most important structural differences between the generated clusters are in the elongated parts, i.e. domains III, IV, and V of EF-G and tRNA of the EF-Tu:tRNA complex. The changes are in agreement with studies showing that the mobility of these fragments is important for the binding of the factors to the ribosome (Agrawal et al. 1998; Valle et al. 2003; Tama et al. 2004; Wriggers et al. 2000). Specifically, when tRNA is delivered by EF-Tu to the ribosome, the tRNA anticodon arm is distorted (Valle et al. 2002; Schuette et al. 2009).Fig. 3


Molecular dynamics of ribosomal elongation factors G and Tu.

Kulczycka K, Długosz M, Trylska J - Eur. Biophys. J. (2010)

Average structures of the three most numerous populations of EF-G (left) and EF-Tu:tRNA (right) derived on the basis of clustering of their RMSD matrices presented in Fig. 3
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045518&req=5

Fig4: Average structures of the three most numerous populations of EF-G (left) and EF-Tu:tRNA (right) derived on the basis of clustering of their RMSD matrices presented in Fig. 3
Mentions: To discern the conformational movements in EF-G and EF-Tu:tRNA, we quantified the changes in RMSD between each trajectory frame. The RMSD-matrices and the cluster analysis are presented in Fig. 3. We observed several clusters with a time-span between 1.5 and 6 ns; 16 groups of different configurations for EF-G (Fig. 3), 22 groups for EF-G:GDP (data not shown), and 11 groups for EF-Tu:tRNA (Fig. 3). The average structures of the most numerous populations of EF-G and EF-Tu:tRNA are shown in Fig. 4. The average RMSD between the structures within each cluster is about 1 Å. The RMSD between structures from different clusters ranges from 2 to 3 Å. In both cases the most important structural differences between the generated clusters are in the elongated parts, i.e. domains III, IV, and V of EF-G and tRNA of the EF-Tu:tRNA complex. The changes are in agreement with studies showing that the mobility of these fragments is important for the binding of the factors to the ribosome (Agrawal et al. 1998; Valle et al. 2003; Tama et al. 2004; Wriggers et al. 2000). Specifically, when tRNA is delivered by EF-Tu to the ribosome, the tRNA anticodon arm is distorted (Valle et al. 2002; Schuette et al. 2009).Fig. 3

Bottom Line: We observed enhanced mobility of EF-G domains III, IV, and V and of tRNA in the EF-Tu:tRNA complex.EF-Tu:GDP complex acquired a configuration different from that found in the crystal structure of EF-Tu with a GTP analogue, showing conformational changes in the switch I and II regions.The calculated electrostatic properties of elongation factors showed no global similarity even though matching electrostatic surface patches were found around the domain I that contacts the ribosome, and in the GDP/GTP binding region.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, Pawinskiego 5A, 02-106 Warsaw, Poland.

ABSTRACT
Translation on the ribosome is controlled by external factors. During polypeptide lengthening, elongation factors EF-Tu and EF-G consecutively interact with the bacterial ribosome. EF-Tu binds and delivers an aminoacyl-tRNA to the ribosomal A site and EF-G helps translocate the tRNAs between their binding sites after the peptide bond is formed. These processes occur at the expense of GTP. EF-Tu:tRNA and EF-G are of similar shape, share a common binding site, and undergo large conformational changes on interaction with the ribosome. To characterize the internal motion of these two elongation factors, we used 25 ns long all-atom molecular dynamics simulations. We observed enhanced mobility of EF-G domains III, IV, and V and of tRNA in the EF-Tu:tRNA complex. EF-Tu:GDP complex acquired a configuration different from that found in the crystal structure of EF-Tu with a GTP analogue, showing conformational changes in the switch I and II regions. The calculated electrostatic properties of elongation factors showed no global similarity even though matching electrostatic surface patches were found around the domain I that contacts the ribosome, and in the GDP/GTP binding region.

Show MeSH