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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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Conformational motions in Hef helicase.Consequent snapshots showing conformational changes in Hef helicase along the relaxation trajectory, highlighted in black in Fig. 2. Snapshots (a–d) correspond to the states at time moments  and  which are indicated by green dots on the trajectory. Both the front view (upper row) and the top view (bottom row) for all conformations are displayed. Absolute distances  in Å between the two motor domains at the respective time moments are indicated under the snapshots in the upper row. In the bottom row, the corresponding distances  are given. Coloring of the domains is the same as in Fig. 1. The backbone  trace representation is employed.
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pone-0021809-g003: Conformational motions in Hef helicase.Consequent snapshots showing conformational changes in Hef helicase along the relaxation trajectory, highlighted in black in Fig. 2. Snapshots (a–d) correspond to the states at time moments and which are indicated by green dots on the trajectory. Both the front view (upper row) and the top view (bottom row) for all conformations are displayed. Absolute distances in Å between the two motor domains at the respective time moments are indicated under the snapshots in the upper row. In the bottom row, the corresponding distances are given. Coloring of the domains is the same as in Fig. 1. The backbone trace representation is employed.

Mentions: To further characterize domain motions, the entire conformational relaxation process, corresponding to one particular trajectory (highlighted black in Fig. 2) can be watched in Video S1 in the backbone-trace representation. Several consequent snapshots from this video are shown in the front and top views in Fig. 3 (a–d). Large-amplitude hinge motions of the mobile motor domain 1 with respect to the other two domains, which are rigidly moving, are clearly seen. During conformational relaxation, the distance between the two motor domains increased from Å to Å so that a large-amplitude conformational change was observed. The distance between the first motor domain and the domain 3 was also increasing from Å to Å.


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

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

Conformational motions in Hef helicase.Consequent snapshots showing conformational changes in Hef helicase along the relaxation trajectory, highlighted in black in Fig. 2. Snapshots (a–d) correspond to the states at time moments  and  which are indicated by green dots on the trajectory. Both the front view (upper row) and the top view (bottom row) for all conformations are displayed. Absolute distances  in Å between the two motor domains at the respective time moments are indicated under the snapshots in the upper row. In the bottom row, the corresponding distances  are given. Coloring of the domains is the same as in Fig. 1. The backbone  trace representation is employed.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0021809-g003: Conformational motions in Hef helicase.Consequent snapshots showing conformational changes in Hef helicase along the relaxation trajectory, highlighted in black in Fig. 2. Snapshots (a–d) correspond to the states at time moments and which are indicated by green dots on the trajectory. Both the front view (upper row) and the top view (bottom row) for all conformations are displayed. Absolute distances in Å between the two motor domains at the respective time moments are indicated under the snapshots in the upper row. In the bottom row, the corresponding distances are given. Coloring of the domains is the same as in Fig. 1. The backbone trace representation is employed.
Mentions: To further characterize domain motions, the entire conformational relaxation process, corresponding to one particular trajectory (highlighted black in Fig. 2) can be watched in Video S1 in the backbone-trace representation. Several consequent snapshots from this video are shown in the front and top views in Fig. 3 (a–d). Large-amplitude hinge motions of the mobile motor domain 1 with respect to the other two domains, which are rigidly moving, are clearly seen. During conformational relaxation, the distance between the two motor domains increased from Å to Å so that a large-amplitude conformational change was observed. The distance between the first motor domain and the domain 3 was also increasing from Å to Å.

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