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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

Temporal changes in the distance between Val23 in one TM1 and Gly26 of the neighboring TM1 with respect to five pairs (a–e). Black and red lines show the results from the unrestrained and restrained water models, respectively. The distance is defined as the distance between the backbone Cα atoms of amino acid residues. f Configuration of two neighboring TM1s in the purple and cyan ribbon representations. Green and brown residues denote Val23 and Gly26, respectively
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Fig8: Temporal changes in the distance between Val23 in one TM1 and Gly26 of the neighboring TM1 with respect to five pairs (a–e). Black and red lines show the results from the unrestrained and restrained water models, respectively. The distance is defined as the distance between the backbone Cα atoms of amino acid residues. f Configuration of two neighboring TM1s in the purple and cyan ribbon representations. Green and brown residues denote Val23 and Gly26, respectively

Mentions: Let us examine the mechanism of increased hydration of the gate after 3.5 ns, in other words, the relationship between hydration and apparently accelerated expansion of the gate, shown in Fig. 4. In the normal model, sliding of TM1 helices at the crossings was observed after an interaction between a water molecule and the exposed backbone oxygen atom of Leu19 occurred [Fig. 3d(ii)]. To understand the role of water molecules in the sliding of TM1 helices, i.e., accelerated gate expansion, we acquired snapshots of the water distribution around the crossing portions of TM1 helices throughout the simulation. A series of these snapshots is presented in Fig. 7a–c. At 3.5 ns, water molecules have wedged into the narrow gap between Val23 in one TM1 and Gly26 of its immediately neighboring TM1. Once this gap was fully occupied by water, Gly26 slipped past the gap to reach the pocket formed by Val16, Leu19, and Ala20. By contrast, the gate underwent minimal conformational change in the MscL model with restrained water movements (Fig. 7d–f). Figure 8 shows how the distance between Val23 on one TM1 and Gly26 from its immediate neighbor changes over time. Results are plotted for ten TM1 pairs: five from the normal model (black lines) and five from the restrained-water MscL model (red lines). In the normal model the distance between TM1s dramatically increased (Fig. 8a, b, e); in the restrained water model, it remained almost constant. This result confirms that entropy-driven water pressure induces conformational changes at the gate. We conclude that water molecules wedging between the helices act as a lubricator to decrease friction between the helices, which would promote the helix sliding toward further expansion of the gate. This may be the first mention on the role of helix sliding accelerated by water in the MscL opening. We may reasonably assume that water dynamics reduce the energy cost of the gate expansion toward channel opening.Fig. 7


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

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

Temporal changes in the distance between Val23 in one TM1 and Gly26 of the neighboring TM1 with respect to five pairs (a–e). Black and red lines show the results from the unrestrained and restrained water models, respectively. The distance is defined as the distance between the backbone Cα atoms of amino acid residues. f Configuration of two neighboring TM1s in the purple and cyan ribbon representations. Green and brown residues denote Val23 and Gly26, respectively
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4562998&req=5

Fig8: Temporal changes in the distance between Val23 in one TM1 and Gly26 of the neighboring TM1 with respect to five pairs (a–e). Black and red lines show the results from the unrestrained and restrained water models, respectively. The distance is defined as the distance between the backbone Cα atoms of amino acid residues. f Configuration of two neighboring TM1s in the purple and cyan ribbon representations. Green and brown residues denote Val23 and Gly26, respectively
Mentions: Let us examine the mechanism of increased hydration of the gate after 3.5 ns, in other words, the relationship between hydration and apparently accelerated expansion of the gate, shown in Fig. 4. In the normal model, sliding of TM1 helices at the crossings was observed after an interaction between a water molecule and the exposed backbone oxygen atom of Leu19 occurred [Fig. 3d(ii)]. To understand the role of water molecules in the sliding of TM1 helices, i.e., accelerated gate expansion, we acquired snapshots of the water distribution around the crossing portions of TM1 helices throughout the simulation. A series of these snapshots is presented in Fig. 7a–c. At 3.5 ns, water molecules have wedged into the narrow gap between Val23 in one TM1 and Gly26 of its immediately neighboring TM1. Once this gap was fully occupied by water, Gly26 slipped past the gap to reach the pocket formed by Val16, Leu19, and Ala20. By contrast, the gate underwent minimal conformational change in the MscL model with restrained water movements (Fig. 7d–f). Figure 8 shows how the distance between Val23 on one TM1 and Gly26 from its immediate neighbor changes over time. Results are plotted for ten TM1 pairs: five from the normal model (black lines) and five from the restrained-water MscL model (red lines). In the normal model the distance between TM1s dramatically increased (Fig. 8a, b, e); in the restrained water model, it remained almost constant. This result confirms that entropy-driven water pressure induces conformational changes at the gate. We conclude that water molecules wedging between the helices act as a lubricator to decrease friction between the helices, which would promote the helix sliding toward further expansion of the gate. This may be the first mention on the role of helix sliding accelerated by water in the MscL opening. We may reasonably assume that water dynamics reduce the energy cost of the gate expansion toward channel opening.Fig. 7

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