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In silico investigation of conformational motions in superfamily 2 helicase proteins.

Flechsig H, Popp D, Mikhailov AS - PLoS ONE (2011)

Bottom Line: Specifically, their responses to mechanical perturbations are analyzed.As we show, such motions are well-organized and have large amplitudes.Their possible roles in the processing of nucleic substrate are discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Physical Chemistry, Fritz Haber Institute of the Max Planck Society, Berlin, Germany. flechsig@fhi-berlin.mpg.de

ABSTRACT
Helicases are motor proteins that play a central role in the metabolism of DNA and RNA in biological cells. Using the energy of ATP molecules, they are able to translocate along the nucleic acids and unwind their duplex structure. They have been extensively characterized in the past and grouped into superfamilies based on structural similarities and sequential motifs. However, their functional aspects and the mechanism of their operation are not yet well understood. Here, we consider three helicases from the major superfamily 2--Hef, Hel308 and XPD--and study their conformational dynamics by using coarse-grained relaxational elastic network models. Specifically, their responses to mechanical perturbations are analyzed. This enables us to identify robust and ordered conformational motions which may underlie the functional activity of these proteins. As we show, such motions are well-organized and have large amplitudes. Their possible roles in the processing of nucleic substrate are discussed.

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Relaxation dynamics of Hel308 helicase.Panels (A) and (B) show the relaxation pattern as a set of 100 trajectories in the space of normalized relative distance changes  and  between the three labels. Each trajectory starts from a different initial deformation that has been generated by applying random static forces globally distributed to all network beads (grey trajectories) or restricted to the beads of the ATP binding site (red trajectories). The viewpoint in (B) is chosen in such a way that the confinement of relaxation trajectories is best seen.
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pone-0021809-g004: Relaxation dynamics of Hel308 helicase.Panels (A) and (B) show the relaxation pattern as a set of 100 trajectories in the space of normalized relative distance changes and between the three labels. Each trajectory starts from a different initial deformation that has been generated by applying random static forces globally distributed to all network beads (grey trajectories) or restricted to the beads of the ATP binding site (red trajectories). The viewpoint in (B) is chosen in such a way that the confinement of relaxation trajectories is best seen.

Mentions: By using the same methods, relaxation dynamics of the Hel308 elastic network has been investigated. Similar to Hef helicase, we found that the trajectories beginning from different initial deformations all returned to the equilibrium conformation with no meta-stable states present (Fig. 4). After short transients, trajectories converged to an attractive bundle along which the relaxation proceeded to the equilibrium conformation of the protein. This behavior was found for both sets of initial deformations, either obtained by applying random forces globally or with the random forces spatially confined to the ATP binding motifs.


In silico investigation of conformational motions in superfamily 2 helicase proteins.

Flechsig H, Popp D, Mikhailov AS - PLoS ONE (2011)

Relaxation dynamics of Hel308 helicase.Panels (A) and (B) show the relaxation pattern as a set of 100 trajectories in the space of normalized relative distance changes  and  between the three labels. Each trajectory starts from a different initial deformation that has been generated by applying random static forces globally distributed to all network beads (grey trajectories) or restricted to the beads of the ATP binding site (red trajectories). The viewpoint in (B) is chosen in such a way that the confinement of relaxation trajectories is best seen.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3139591&req=5

pone-0021809-g004: Relaxation dynamics of Hel308 helicase.Panels (A) and (B) show the relaxation pattern as a set of 100 trajectories in the space of normalized relative distance changes and between the three labels. Each trajectory starts from a different initial deformation that has been generated by applying random static forces globally distributed to all network beads (grey trajectories) or restricted to the beads of the ATP binding site (red trajectories). The viewpoint in (B) is chosen in such a way that the confinement of relaxation trajectories is best seen.
Mentions: By using the same methods, relaxation dynamics of the Hel308 elastic network has been investigated. Similar to Hef helicase, we found that the trajectories beginning from different initial deformations all returned to the equilibrium conformation with no meta-stable states present (Fig. 4). After short transients, trajectories converged to an attractive bundle along which the relaxation proceeded to the equilibrium conformation of the protein. This behavior was found for both sets of initial deformations, either obtained by applying random forces globally or with the random forces spatially confined to the ATP binding motifs.

Bottom Line: Specifically, their responses to mechanical perturbations are analyzed.As we show, such motions are well-organized and have large amplitudes.Their possible roles in the processing of nucleic substrate are discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Physical Chemistry, Fritz Haber Institute of the Max Planck Society, Berlin, Germany. flechsig@fhi-berlin.mpg.de

ABSTRACT
Helicases are motor proteins that play a central role in the metabolism of DNA and RNA in biological cells. Using the energy of ATP molecules, they are able to translocate along the nucleic acids and unwind their duplex structure. They have been extensively characterized in the past and grouped into superfamilies based on structural similarities and sequential motifs. However, their functional aspects and the mechanism of their operation are not yet well understood. Here, we consider three helicases from the major superfamily 2--Hef, Hel308 and XPD--and study their conformational dynamics by using coarse-grained relaxational elastic network models. Specifically, their responses to mechanical perturbations are analyzed. This enables us to identify robust and ordered conformational motions which may underlie the functional activity of these proteins. As we show, such motions are well-organized and have large amplitudes. Their possible roles in the processing of nucleic substrate are discussed.

Show MeSH