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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 MscL structural changes as membrane tension increases in the unrestrained water (normal) 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 (ii) are taken at 0, 3, and 5 ns, respectively. Eco-MscL is shown in the ribbon representation; TM1 and TM2 helices are colored blue and red, respectively. The lipid and water molecules are excluded in rowsa and b but water molecules are shown in rowc
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Fig3: Snapshots of MscL structural changes as membrane tension increases in the unrestrained water (normal) 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 (ii) are taken at 0, 3, and 5 ns, respectively. Eco-MscL is shown in the ribbon representation; TM1 and TM2 helices are colored blue and red, respectively. The lipid and water molecules are excluded in rowsa and b but water molecules are shown in rowc

Mentions: During the 50-ns equilibration period, MscL maintained its closed state in which the pore was lined with five TM1 helices. Immediately neighboring helices cross each other in the inner leaflet of the bilayer to form the most constricted pentagon-shaped structure called the gate (Fig. 1a, b). Gly22 in the TM1 helix of a subunit fits into a pocket formed by Val16, Leu19, and Ala20 from the immediately neighboring subunit. This hydrophobic interaction between neighboring TM1s stabilizes the closed state of the gate, thus being called the hydrophobic lock (Fig. 1c). Because of the small size of the closed gate and hydrophobic nature of its constituent amino acids (Leu19–Val23), no water was detected inside the gate, i.e., the gate was stably dehydrated in the closed state [Fig. 3c(i)].Fig. 3


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 MscL structural changes as membrane tension increases in the unrestrained water (normal) 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 (ii) are taken at 0, 3, and 5 ns, respectively. Eco-MscL is shown in the ribbon representation; TM1 and TM2 helices are colored blue and red, respectively. The lipid and water molecules are excluded in rowsa and b but water molecules are shown in rowc
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Snapshots of MscL structural changes as membrane tension increases in the unrestrained water (normal) 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 (ii) are taken at 0, 3, and 5 ns, respectively. Eco-MscL is shown in the ribbon representation; TM1 and TM2 helices are colored blue and red, respectively. The lipid and water molecules are excluded in rowsa and b but water molecules are shown in rowc
Mentions: During the 50-ns equilibration period, MscL maintained its closed state in which the pore was lined with five TM1 helices. Immediately neighboring helices cross each other in the inner leaflet of the bilayer to form the most constricted pentagon-shaped structure called the gate (Fig. 1a, b). Gly22 in the TM1 helix of a subunit fits into a pocket formed by Val16, Leu19, and Ala20 from the immediately neighboring subunit. This hydrophobic interaction between neighboring TM1s stabilizes the closed state of the gate, thus being called the hydrophobic lock (Fig. 1c). Because of the small size of the closed gate and hydrophobic nature of its constituent amino acids (Leu19–Val23), no water was detected inside the gate, i.e., the gate was stably dehydrated in the closed state [Fig. 3c(i)].Fig. 3

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