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Dynamics of the Glycophorin A Dimer in Membranes of Native-Like Composition Uncovered by Coarse-Grained Molecular Dynamics Simulations.

Flinner N, Schleiff E - PLoS ONE (2015)

Bottom Line: It was documented that molecular dynamics simulations of an idealized plasma membrane model result in formation of membrane areas where either saturated lipids and cholesterol (liquid-ordered character, Lo) or unsaturated lipids (liquid-disordered character, Ld) were enriched.Moreover, it is an important factor for the reproduction of the dynamic behavior of the protein found in its native environment.Therefore, we present structural information on the glycophorin A dimer distribution in the plasma membrane in the absence of other factors like e.g. lipid anchors in a coarse grain resolution.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences, Molecular Cell Biology of Plants, Goethe University, Max von Laue Str. 9, 60438, Frankfurt/Main, Germany.

ABSTRACT
Membranes are central for cells as borders to the environment or intracellular organelle definition. They are composed of and harbor different molecules like various lipid species and sterols, and they are generally crowded with proteins. The membrane system is very dynamic and components show lateral, rotational and translational diffusion. The consequence of the latter is that phase separation can occur in membranes in vivo and in vitro. It was documented that molecular dynamics simulations of an idealized plasma membrane model result in formation of membrane areas where either saturated lipids and cholesterol (liquid-ordered character, Lo) or unsaturated lipids (liquid-disordered character, Ld) were enriched. Furthermore, current discussions favor the idea that proteins are sorted into the liquid-disordered phase of model membranes, but experimental support for the behavior of isolated proteins in native membranes is sparse. To gain insight into the protein behavior we built a model of the red blood cell membrane with integrated glycophorin A dimer. The sorting and the dynamics of the dimer were subsequently explored by coarse-grained molecular dynamics simulations. In addition, we inspected the impact of lipid head groups and the presence of cholesterol within the membrane on the dynamics of the dimer within the membrane. We observed that cholesterol is important for the formation of membrane areas with Lo and Ld character. Moreover, it is an important factor for the reproduction of the dynamic behavior of the protein found in its native environment. The protein dimer was exclusively sorted into the domain of Ld character in the model red blood cell plasma membrane. Therefore, we present structural information on the glycophorin A dimer distribution in the plasma membrane in the absence of other factors like e.g. lipid anchors in a coarse grain resolution.

No MeSH data available.


Related in: MedlinePlus

Interaction of lipids and protein in the RBC plasma membrane.(A) The maximal time (y-axis) a lipid is adjacent to the protein of each of the ten simulations is plotted for the different lipid species. The head group is given below, the fatty acid is color coded. Lipids of the outer and inner leaflet are shown separately. (B) Plotted are the first (distance < 0.658 nm), second (0.658 nm < distance < 0.918 nm) and third (0.918 nm < distance < 1.178 nm) hydration shell around the protein for the outer (upper part of the circle) and inner leaflet (lower part of the circle). The head group is given and the color of the label indicates the fatty acid. For each lipid it is given in color code, if its occurrence in the respective hydration shell is increased (green) or decreased (red) in comparison to the lipid frequency in the corresponding leaflet.
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pone.0133999.g003: Interaction of lipids and protein in the RBC plasma membrane.(A) The maximal time (y-axis) a lipid is adjacent to the protein of each of the ten simulations is plotted for the different lipid species. The head group is given below, the fatty acid is color coded. Lipids of the outer and inner leaflet are shown separately. (B) Plotted are the first (distance < 0.658 nm), second (0.658 nm < distance < 0.918 nm) and third (0.918 nm < distance < 1.178 nm) hydration shell around the protein for the outer (upper part of the circle) and inner leaflet (lower part of the circle). The head group is given and the color of the label indicates the fatty acid. For each lipid it is given in color code, if its occurrence in the respective hydration shell is increased (green) or decreased (red) in comparison to the lipid frequency in the corresponding leaflet.

Mentions: Focusing on the interaction of the protein with the lipids and cholesterol it becomes obvious that cholesterol is attached to the protein for the longest time when compared to other lipids of the leaflet (Fig 3A) and it is proven that these cholesterol molecules diffuse freely to the protein and are not attached to the protein at the beginning of the simulation (S5 Fig). Additionally, cholesterol is preferred in the first hydration shell around the protein on both leaflets (Fig 3B). This behavior is independent of the lipid head group distribution, because the same result is observed for the PC+CHOL membrane (S6 and S7 Figs). These findings are in good agreement to the experimental observation that in vesicles containing DMPC and cholesterol the latter is enriched in the vicinity of GpA [46,47]. Furthermore, the observed close vicinity of cholesterol to the transmembrane region fits to the influence of cholesterol on the dynamics of the protein as well (Fig 2). Analyzing which residues interact with lipids we noticed that the side chain beads of V84 and I88 interact nearly the whole simulation time (>95%) with cholesterol, a phenomenon which is not observed for other lipids and other residues of the protein. Interestingly both residues flank the GxxxGxxxT motif of the NMR interface and both residues are able to interact with one cholesterol molecule (S8 Fig), which is found often during the simulation. Both residues are not involved in the interface which is formed in cluster 40 (Fig 2C).


Dynamics of the Glycophorin A Dimer in Membranes of Native-Like Composition Uncovered by Coarse-Grained Molecular Dynamics Simulations.

Flinner N, Schleiff E - PLoS ONE (2015)

Interaction of lipids and protein in the RBC plasma membrane.(A) The maximal time (y-axis) a lipid is adjacent to the protein of each of the ten simulations is plotted for the different lipid species. The head group is given below, the fatty acid is color coded. Lipids of the outer and inner leaflet are shown separately. (B) Plotted are the first (distance < 0.658 nm), second (0.658 nm < distance < 0.918 nm) and third (0.918 nm < distance < 1.178 nm) hydration shell around the protein for the outer (upper part of the circle) and inner leaflet (lower part of the circle). The head group is given and the color of the label indicates the fatty acid. For each lipid it is given in color code, if its occurrence in the respective hydration shell is increased (green) or decreased (red) in comparison to the lipid frequency in the corresponding leaflet.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4519189&req=5

pone.0133999.g003: Interaction of lipids and protein in the RBC plasma membrane.(A) The maximal time (y-axis) a lipid is adjacent to the protein of each of the ten simulations is plotted for the different lipid species. The head group is given below, the fatty acid is color coded. Lipids of the outer and inner leaflet are shown separately. (B) Plotted are the first (distance < 0.658 nm), second (0.658 nm < distance < 0.918 nm) and third (0.918 nm < distance < 1.178 nm) hydration shell around the protein for the outer (upper part of the circle) and inner leaflet (lower part of the circle). The head group is given and the color of the label indicates the fatty acid. For each lipid it is given in color code, if its occurrence in the respective hydration shell is increased (green) or decreased (red) in comparison to the lipid frequency in the corresponding leaflet.
Mentions: Focusing on the interaction of the protein with the lipids and cholesterol it becomes obvious that cholesterol is attached to the protein for the longest time when compared to other lipids of the leaflet (Fig 3A) and it is proven that these cholesterol molecules diffuse freely to the protein and are not attached to the protein at the beginning of the simulation (S5 Fig). Additionally, cholesterol is preferred in the first hydration shell around the protein on both leaflets (Fig 3B). This behavior is independent of the lipid head group distribution, because the same result is observed for the PC+CHOL membrane (S6 and S7 Figs). These findings are in good agreement to the experimental observation that in vesicles containing DMPC and cholesterol the latter is enriched in the vicinity of GpA [46,47]. Furthermore, the observed close vicinity of cholesterol to the transmembrane region fits to the influence of cholesterol on the dynamics of the protein as well (Fig 2). Analyzing which residues interact with lipids we noticed that the side chain beads of V84 and I88 interact nearly the whole simulation time (>95%) with cholesterol, a phenomenon which is not observed for other lipids and other residues of the protein. Interestingly both residues flank the GxxxGxxxT motif of the NMR interface and both residues are able to interact with one cholesterol molecule (S8 Fig), which is found often during the simulation. Both residues are not involved in the interface which is formed in cluster 40 (Fig 2C).

Bottom Line: It was documented that molecular dynamics simulations of an idealized plasma membrane model result in formation of membrane areas where either saturated lipids and cholesterol (liquid-ordered character, Lo) or unsaturated lipids (liquid-disordered character, Ld) were enriched.Moreover, it is an important factor for the reproduction of the dynamic behavior of the protein found in its native environment.Therefore, we present structural information on the glycophorin A dimer distribution in the plasma membrane in the absence of other factors like e.g. lipid anchors in a coarse grain resolution.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences, Molecular Cell Biology of Plants, Goethe University, Max von Laue Str. 9, 60438, Frankfurt/Main, Germany.

ABSTRACT
Membranes are central for cells as borders to the environment or intracellular organelle definition. They are composed of and harbor different molecules like various lipid species and sterols, and they are generally crowded with proteins. The membrane system is very dynamic and components show lateral, rotational and translational diffusion. The consequence of the latter is that phase separation can occur in membranes in vivo and in vitro. It was documented that molecular dynamics simulations of an idealized plasma membrane model result in formation of membrane areas where either saturated lipids and cholesterol (liquid-ordered character, Lo) or unsaturated lipids (liquid-disordered character, Ld) were enriched. Furthermore, current discussions favor the idea that proteins are sorted into the liquid-disordered phase of model membranes, but experimental support for the behavior of isolated proteins in native membranes is sparse. To gain insight into the protein behavior we built a model of the red blood cell membrane with integrated glycophorin A dimer. The sorting and the dynamics of the dimer were subsequently explored by coarse-grained molecular dynamics simulations. In addition, we inspected the impact of lipid head groups and the presence of cholesterol within the membrane on the dynamics of the dimer within the membrane. We observed that cholesterol is important for the formation of membrane areas with Lo and Ld character. Moreover, it is an important factor for the reproduction of the dynamic behavior of the protein found in its native environment. The protein dimer was exclusively sorted into the domain of Ld character in the model red blood cell plasma membrane. Therefore, we present structural information on the glycophorin A dimer distribution in the plasma membrane in the absence of other factors like e.g. lipid anchors in a coarse grain resolution.

No MeSH data available.


Related in: MedlinePlus