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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.

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Left: Secondary structure model of EF-G in the complex with GDP and Mg2+ (PDB code 1FNM); domain I(G), residues 1–280 (red); insert (G′), residues 158–253 (yellow); domain II, residues 289–391 (dark blue); domain III, residues 404–482 (orange); domain IV, residues 483–603, 675–689 (green); domain V, residues 604–673 (brown). Right: EF-Tu complexed with aa-tRNA, GDP, and Mg2+ (based on the PDB code 1TTT); domain I(G), residues 1–211 (red); domain II, residues 220–311 (dark blue); domain III, residues 312–405 (light blue); aa-tRNA is divided into the acceptor stem (orange), anticodon arm (green), and T-arm (brown). Domains I(G) and II of EF-Tu and EF-G are homologous and common for GTPases
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Fig1: Left: Secondary structure model of EF-G in the complex with GDP and Mg2+ (PDB code 1FNM); domain I(G), residues 1–280 (red); insert (G′), residues 158–253 (yellow); domain II, residues 289–391 (dark blue); domain III, residues 404–482 (orange); domain IV, residues 483–603, 675–689 (green); domain V, residues 604–673 (brown). Right: EF-Tu complexed with aa-tRNA, GDP, and Mg2+ (based on the PDB code 1TTT); domain I(G), residues 1–211 (red); domain II, residues 220–311 (dark blue); domain III, residues 312–405 (light blue); aa-tRNA is divided into the acceptor stem (orange), anticodon arm (green), and T-arm (brown). Domains I(G) and II of EF-Tu and EF-G are homologous and common for GTPases

Mentions: EF-G is composed of five domains and EF-Tu of three (Fig. 1). Domain I (or G) of both factors contains the GTP (or GDP) binding site and domain II forms a unique β-barrel. The I domain of EF-G includes an insertion—the G′ subdomain—that is exclusive for EF-G and does not exist in EF-Tu. The three-dimensional structure of EF-G closely resembles that of the complex between EF-Tu and tRNA (Fig. 1). Both structures are of elongated shape. EF-G domains I and II are homologous with EF-Tu, and EF-G domains III, IV, and V adopt the shape of tRNA (Gudkov 2001). Such structural correspondence of molecular fragments is an example of molecular mimicry (Nyborg et al. 1996); the protein domains evolved so that they can mimic the shape of the tRNA molecule. The crystal structure of the GDP-inactive form of EF-G resembles the GTP-active structure of the ternary complex (Nyborg et al. 1996; Sergiev et al. 2005). EF-G and the ternary complex bind at the interface of the ribosomal subunits in an elongated but tight cleft close to the L11 protein of the 50S subunit (Gao et al. 2009; Schmeing et al. 2009).Fig. 1


Molecular dynamics of ribosomal elongation factors G and Tu.

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

Left: Secondary structure model of EF-G in the complex with GDP and Mg2+ (PDB code 1FNM); domain I(G), residues 1–280 (red); insert (G′), residues 158–253 (yellow); domain II, residues 289–391 (dark blue); domain III, residues 404–482 (orange); domain IV, residues 483–603, 675–689 (green); domain V, residues 604–673 (brown). Right: EF-Tu complexed with aa-tRNA, GDP, and Mg2+ (based on the PDB code 1TTT); domain I(G), residues 1–211 (red); domain II, residues 220–311 (dark blue); domain III, residues 312–405 (light blue); aa-tRNA is divided into the acceptor stem (orange), anticodon arm (green), and T-arm (brown). Domains I(G) and II of EF-Tu and EF-G are homologous and common for GTPases
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3045518&req=5

Fig1: Left: Secondary structure model of EF-G in the complex with GDP and Mg2+ (PDB code 1FNM); domain I(G), residues 1–280 (red); insert (G′), residues 158–253 (yellow); domain II, residues 289–391 (dark blue); domain III, residues 404–482 (orange); domain IV, residues 483–603, 675–689 (green); domain V, residues 604–673 (brown). Right: EF-Tu complexed with aa-tRNA, GDP, and Mg2+ (based on the PDB code 1TTT); domain I(G), residues 1–211 (red); domain II, residues 220–311 (dark blue); domain III, residues 312–405 (light blue); aa-tRNA is divided into the acceptor stem (orange), anticodon arm (green), and T-arm (brown). Domains I(G) and II of EF-Tu and EF-G are homologous and common for GTPases
Mentions: EF-G is composed of five domains and EF-Tu of three (Fig. 1). Domain I (or G) of both factors contains the GTP (or GDP) binding site and domain II forms a unique β-barrel. The I domain of EF-G includes an insertion—the G′ subdomain—that is exclusive for EF-G and does not exist in EF-Tu. The three-dimensional structure of EF-G closely resembles that of the complex between EF-Tu and tRNA (Fig. 1). Both structures are of elongated shape. EF-G domains I and II are homologous with EF-Tu, and EF-G domains III, IV, and V adopt the shape of tRNA (Gudkov 2001). Such structural correspondence of molecular fragments is an example of molecular mimicry (Nyborg et al. 1996); the protein domains evolved so that they can mimic the shape of the tRNA molecule. The crystal structure of the GDP-inactive form of EF-G resembles the GTP-active structure of the ternary complex (Nyborg et al. 1996; Sergiev et al. 2005). EF-G and the ternary complex bind at the interface of the ribosomal subunits in an elongated but tight cleft close to the L11 protein of the 50S subunit (Gao et al. 2009; Schmeing et al. 2009).Fig. 1

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.

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