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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

Side (a) and top (b) views of our simulation model comprising the E. coli MscL, POPC, and water molecules. MscL is shown in ribbon view with different colors for each subunit. The water molecules are shown in red (oxygen atoms) and white (hydrogen atoms). The brown atoms in the space-filling drawing are the phosphate atoms of individual lipid molecules
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Fig2: Side (a) and top (b) views of our simulation model comprising the E. coli MscL, POPC, and water molecules. MscL is shown in ribbon view with different colors for each subunit. The water molecules are shown in red (oxygen atoms) and white (hydrogen atoms). The brown atoms in the space-filling drawing are the phosphate atoms of individual lipid molecules

Mentions: In this study, we first modeled MscL from Escherichia coli (E. coli MscL) in the closed state with S1 helices running parallel to the cytoplasmic membrane surface (Fig. 1). This model was based on the structure of MscL from M. Tuberculosis solved in 2007 (PDB code: 2OAR). The residues in the cytoplasmic region beyond Ala110 of the Eco-MscL, which have been suggested not to be essential for MscL gating, have been excised to reduce the total size of the system (Ajouz et al. 2000). The E. coli MscL model in a fully hydrated palmitoyl-oleoyl phosphatidylcholine (POPC) bilayer, which was utilized in our previous study, was solvated to place water molecules, as shown in Fig. 2, minimized over 10,000 steps with a fixed protein backbone, and then equilibrated for 50 ns under unrestrained conditions (351 lipids, 66 sodium and 71 chloride ions, approximately 23,000 water molecules, and approximately 125,000 atoms in total) (Grubmüller 1996; Sawada et al. 2012). After a 50-ns equilibration, opening simulations were performed with and without restraining lateral movements of the water molecules at the vapor–water interfaces of the periplasmic and cytoplasmic sides of the dewetted gate. In this study, the simulations with and without water restraints are denoted as restrained water and unrestrained water, respectively.Fig. 1


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

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

Side (a) and top (b) views of our simulation model comprising the E. coli MscL, POPC, and water molecules. MscL is shown in ribbon view with different colors for each subunit. The water molecules are shown in red (oxygen atoms) and white (hydrogen atoms). The brown atoms in the space-filling drawing are the phosphate atoms of individual lipid molecules
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Side (a) and top (b) views of our simulation model comprising the E. coli MscL, POPC, and water molecules. MscL is shown in ribbon view with different colors for each subunit. The water molecules are shown in red (oxygen atoms) and white (hydrogen atoms). The brown atoms in the space-filling drawing are the phosphate atoms of individual lipid molecules
Mentions: In this study, we first modeled MscL from Escherichia coli (E. coli MscL) in the closed state with S1 helices running parallel to the cytoplasmic membrane surface (Fig. 1). This model was based on the structure of MscL from M. Tuberculosis solved in 2007 (PDB code: 2OAR). The residues in the cytoplasmic region beyond Ala110 of the Eco-MscL, which have been suggested not to be essential for MscL gating, have been excised to reduce the total size of the system (Ajouz et al. 2000). The E. coli MscL model in a fully hydrated palmitoyl-oleoyl phosphatidylcholine (POPC) bilayer, which was utilized in our previous study, was solvated to place water molecules, as shown in Fig. 2, minimized over 10,000 steps with a fixed protein backbone, and then equilibrated for 50 ns under unrestrained conditions (351 lipids, 66 sodium and 71 chloride ions, approximately 23,000 water molecules, and approximately 125,000 atoms in total) (Grubmüller 1996; Sawada et al. 2012). After a 50-ns equilibration, opening simulations were performed with and without restraining lateral movements of the water molecules at the vapor–water interfaces of the periplasmic and cytoplasmic sides of the dewetted gate. In this study, the simulations with and without water restraints are denoted as restrained water and unrestrained water, respectively.Fig. 1

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