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Molecular dynamics study on protein-water interplay in the mechanogating of the bacterial mechanosensitive channel MscL.

Sawada Y, Sokabe M - Eur. Biophys. J. (2015)

Bottom Line: The gating behaviors in this model and the normal MscL model, in which water movements are unrestrained, are compared.This suggests that gate opening relies on a conformational change initiated by wetting.The penetrated water weakens the hydrophobic interaction between neighboring transmembrane inner helices called the "hydrophobic lock" by wedging into the space between their interacting portions.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

ABSTRACT
One of the goals of mechanosensitive channel (MSC) studies is to understand the underlying molecular and biophysical mechanisms of the mechano-gating process from force sensing to gate opening. We focus on the latter process and investigate the role of water in the bacterial MSC MscL, which is activated by membrane tension. We analyze the interplay between water and the gate-constituting amino acids, Leu19-Gly26, through molecular dynamics simulations. To highlight the role of water, specifically hydration of the gate, in MscL gating, we restrain lateral movements of the water molecules along the water-vapor interfaces at the top and bottom of the vapor bubble, plugging the closed gate. The gating behaviors in this model and the normal MscL model, in which water movements are unrestrained, are compared. In the normal model, increased membrane tension breaks the hydrogen bond between Leu19 and Val 23 of the inner helix, exposing the backbone carbonyl oxygen of Leu19 to the water-accessible lumen side of the gate. Associated with this activity, water comes to access the vapor region and stably interacts with the carbonyl oxygen to induce a dewetting to wetting transition that facilitates gate expansion toward channel opening. By contrast, in the water-restrained model, carbonyl oxygen is also exposed, but no further conformational changes occur at the gate. This suggests that gate opening relies on a conformational change initiated by wetting. The penetrated water weakens the hydrophobic interaction between neighboring transmembrane inner helices called the "hydrophobic lock" by wedging into the space between their interacting portions.

No MeSH data available.


Related in: MedlinePlus

Snapshots of structural changes in MscL under increased tension in the restrained water simulation. aTop views, b corresponding side views, c water molecules around the gate, and d enlarged conformational changes at the gate of a TM1 helix, showing kinking and exposure of the backbone carbonyl oxygen atom of Leu19. Columns (i), (ii), and (iii) are taken 0, 3, and 5 ns, respectively. Eco-MscL is shown in the ribbon representation, with the TM1 and TM2 helices colored blue and red, respectively. The lipid and water molecules are excluded in rowsa and b but are shown in rowc
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Fig5: Snapshots of structural changes in MscL under increased tension in the restrained water simulation. aTop views, b corresponding side views, c water molecules around the gate, and d enlarged conformational changes at the gate of a TM1 helix, showing kinking and exposure of the backbone carbonyl oxygen atom of Leu19. Columns (i), (ii), and (iii) are taken 0, 3, and 5 ns, respectively. Eco-MscL is shown in the ribbon representation, with the TM1 and TM2 helices colored blue and red, respectively. The lipid and water molecules are excluded in rowsa and b but are shown in rowc

Mentions: As described in the above subsection, breakage of the hydrogen bond between Leu19 and Val23 appears crucial to wetting and accelerated expansion of the gate with dramatic increases in the number of water molecules in the gate (Fig. 4). However, the relationship between the wetting and the accelerated gate expansion, whether these events are causally related, is not clear. Assuming that gate expansion is induced by water dynamics, we restrained the water movements around the gate, thereby eliminated their contribution to the gate expansion. After a 50-ns equilibration of the system, we restrained the lateral movement of water molecules forming the water–vapor interfaces and performed MscL opening simulations identical to the normal model. Figure 5 depicts conformational changes in the water-restrained MscL model induced by increased membrane tension. Early in the simulation time, the MscL protein behaved similarly to the normal MscL (with unrestrained water movements); the helices were tilted, and TM1 became kinked near Leu19, exposing the carbonyl oxygen of Leu19 to the pore lumen [Fig. 5d(ii, iii)]. However, no further expansion of the gate was observed (Fig. 5a, b), probably because the gate region was not allowed to interact with water (Figs. 4, 5). Comparing Figs. 3c and 5c, we infer that the opening mechanism of MscL is initiated by exposing the oxygen atom of Leu19 to the pore lumen, regardless of any interaction between water and the gate region.Fig. 5


Molecular dynamics study on protein-water interplay in the mechanogating of the bacterial mechanosensitive channel MscL.

Sawada Y, Sokabe M - Eur. Biophys. J. (2015)

Snapshots of structural changes in MscL under increased tension in the restrained water simulation. aTop views, b corresponding side views, c water molecules around the gate, and d enlarged conformational changes at the gate of a TM1 helix, showing kinking and exposure of the backbone carbonyl oxygen atom of Leu19. Columns (i), (ii), and (iii) are taken 0, 3, and 5 ns, respectively. Eco-MscL is shown in the ribbon representation, with the TM1 and TM2 helices colored blue and red, respectively. The lipid and water molecules are excluded in rowsa and b but are shown in rowc
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562998&req=5

Fig5: Snapshots of structural changes in MscL under increased tension in the restrained water simulation. aTop views, b corresponding side views, c water molecules around the gate, and d enlarged conformational changes at the gate of a TM1 helix, showing kinking and exposure of the backbone carbonyl oxygen atom of Leu19. Columns (i), (ii), and (iii) are taken 0, 3, and 5 ns, respectively. Eco-MscL is shown in the ribbon representation, with the TM1 and TM2 helices colored blue and red, respectively. The lipid and water molecules are excluded in rowsa and b but are shown in rowc
Mentions: As described in the above subsection, breakage of the hydrogen bond between Leu19 and Val23 appears crucial to wetting and accelerated expansion of the gate with dramatic increases in the number of water molecules in the gate (Fig. 4). However, the relationship between the wetting and the accelerated gate expansion, whether these events are causally related, is not clear. Assuming that gate expansion is induced by water dynamics, we restrained the water movements around the gate, thereby eliminated their contribution to the gate expansion. After a 50-ns equilibration of the system, we restrained the lateral movement of water molecules forming the water–vapor interfaces and performed MscL opening simulations identical to the normal model. Figure 5 depicts conformational changes in the water-restrained MscL model induced by increased membrane tension. Early in the simulation time, the MscL protein behaved similarly to the normal MscL (with unrestrained water movements); the helices were tilted, and TM1 became kinked near Leu19, exposing the carbonyl oxygen of Leu19 to the pore lumen [Fig. 5d(ii, iii)]. However, no further expansion of the gate was observed (Fig. 5a, b), probably because the gate region was not allowed to interact with water (Figs. 4, 5). Comparing Figs. 3c and 5c, we infer that the opening mechanism of MscL is initiated by exposing the oxygen atom of Leu19 to the pore lumen, regardless of any interaction between water and the gate region.Fig. 5

Bottom Line: The gating behaviors in this model and the normal MscL model, in which water movements are unrestrained, are compared.This suggests that gate opening relies on a conformational change initiated by wetting.The penetrated water weakens the hydrophobic interaction between neighboring transmembrane inner helices called the "hydrophobic lock" by wedging into the space between their interacting portions.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

ABSTRACT
One of the goals of mechanosensitive channel (MSC) studies is to understand the underlying molecular and biophysical mechanisms of the mechano-gating process from force sensing to gate opening. We focus on the latter process and investigate the role of water in the bacterial MSC MscL, which is activated by membrane tension. We analyze the interplay between water and the gate-constituting amino acids, Leu19-Gly26, through molecular dynamics simulations. To highlight the role of water, specifically hydration of the gate, in MscL gating, we restrain lateral movements of the water molecules along the water-vapor interfaces at the top and bottom of the vapor bubble, plugging the closed gate. The gating behaviors in this model and the normal MscL model, in which water movements are unrestrained, are compared. In the normal model, increased membrane tension breaks the hydrogen bond between Leu19 and Val 23 of the inner helix, exposing the backbone carbonyl oxygen of Leu19 to the water-accessible lumen side of the gate. Associated with this activity, water comes to access the vapor region and stably interacts with the carbonyl oxygen to induce a dewetting to wetting transition that facilitates gate expansion toward channel opening. By contrast, in the water-restrained model, carbonyl oxygen is also exposed, but no further conformational changes occur at the gate. This suggests that gate opening relies on a conformational change initiated by wetting. The penetrated water weakens the hydrophobic interaction between neighboring transmembrane inner helices called the "hydrophobic lock" by wedging into the space between their interacting portions.

No MeSH data available.


Related in: MedlinePlus