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"SP-G", a putative new surfactant protein--tissue localization and 3D structure.

Rausch F, Schicht M, Paulsen F, Ngueya I, Bräuer L, Brandt W - PLoS ONE (2012)

Bottom Line: In this work, computational chemistry and molecular-biological methods were combined to localize and characterize SP-G.With the help of a protein structure model, specific antibodies were obtained which allowed the detection of SP-G not only on mRNA but also on protein level.This includes also the possibility of interactions with lipid systems and with that, a potential surface-regulatory feature of SP-G.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Halle, Germany.

ABSTRACT
Surfactant proteins (SP) are well known from human lung. These proteins assist the formation of a monolayer of surface-active phospholipids at the liquid-air interface of the alveolar lining, play a major role in lowering the surface tension of interfaces, and have functions in innate and adaptive immune defense. During recent years it became obvious that SPs are also part of other tissues and fluids such as tear fluid, gingiva, saliva, the nasolacrimal system, and kidney. Recently, a putative new surfactant protein (SFTA2 or SP-G) was identified, which has no sequence or structural identity to the already know surfactant proteins. In this work, computational chemistry and molecular-biological methods were combined to localize and characterize SP-G. With the help of a protein structure model, specific antibodies were obtained which allowed the detection of SP-G not only on mRNA but also on protein level. The localization of this protein in different human tissues, sequence based prediction tools for posttranslational modifications and molecular dynamic simulations reveal that SP-G has physicochemical properties similar to the already known surfactant proteins B and C. This includes also the possibility of interactions with lipid systems and with that, a potential surface-regulatory feature of SP-G. In conclusion, the results indicate SP-G as a new surfactant protein which represents an until now unknown surfactant protein class.

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Related in: MedlinePlus

SP-G model and DPPC monolayer after a 50 ns MD simulation.The protein is shown in ribbon presentation (α-helices: blue, β-sheets: red, turns: green, coil: cyan) and the lipids with a yellow van der Waals surface. The N-terminal signal peptide and the α-helix 42–56 are interacting with the lipid surface, stabilizing the protein structure.
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pone-0047789-g011: SP-G model and DPPC monolayer after a 50 ns MD simulation.The protein is shown in ribbon presentation (α-helices: blue, β-sheets: red, turns: green, coil: cyan) and the lipids with a yellow van der Waals surface. The N-terminal signal peptide and the α-helix 42–56 are interacting with the lipid surface, stabilizing the protein structure.

Mentions: Four MD simulations of 50 ns length each were performed for the protein model without posttranslational modifications, starting from different orientations of the protein between the monolayers. The protein model moved in direction to one of the monolayers in all simulations, mostly interacting with the N-terminal signal peptide first. Thereby, the signal peptide is aligned parallel to the lipid surface after reaching the polar lipid head groups. It has to be noted that the α-helical conformation of this part is lost during this process. This position of the protein also allows the interaction of the α-helix 42–56 with the monolayer in a parallel orientation. This agglomeration process took between 2 and 10 ns of simulation time. The interactions between protein and lipids are stabilized during the remaining simulation time, leading to a very stable complex of protein and lipids. This stability is visible in both the protein backbone RMSD (black plot, Figure 9) and area per lipid plot (black plot, Figure 10). During this steady phase after about 15 ns, the hydrophobic part of the signal peptide is penetrating deeper into the lipid layer (Figure 11). There, the clearly visible interaction contact between the protein model and the lipid layer after 50 ns of MD simulation is shown.


"SP-G", a putative new surfactant protein--tissue localization and 3D structure.

Rausch F, Schicht M, Paulsen F, Ngueya I, Bräuer L, Brandt W - PLoS ONE (2012)

SP-G model and DPPC monolayer after a 50 ns MD simulation.The protein is shown in ribbon presentation (α-helices: blue, β-sheets: red, turns: green, coil: cyan) and the lipids with a yellow van der Waals surface. The N-terminal signal peptide and the α-helix 42–56 are interacting with the lipid surface, stabilizing the protein structure.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475697&req=5

pone-0047789-g011: SP-G model and DPPC monolayer after a 50 ns MD simulation.The protein is shown in ribbon presentation (α-helices: blue, β-sheets: red, turns: green, coil: cyan) and the lipids with a yellow van der Waals surface. The N-terminal signal peptide and the α-helix 42–56 are interacting with the lipid surface, stabilizing the protein structure.
Mentions: Four MD simulations of 50 ns length each were performed for the protein model without posttranslational modifications, starting from different orientations of the protein between the monolayers. The protein model moved in direction to one of the monolayers in all simulations, mostly interacting with the N-terminal signal peptide first. Thereby, the signal peptide is aligned parallel to the lipid surface after reaching the polar lipid head groups. It has to be noted that the α-helical conformation of this part is lost during this process. This position of the protein also allows the interaction of the α-helix 42–56 with the monolayer in a parallel orientation. This agglomeration process took between 2 and 10 ns of simulation time. The interactions between protein and lipids are stabilized during the remaining simulation time, leading to a very stable complex of protein and lipids. This stability is visible in both the protein backbone RMSD (black plot, Figure 9) and area per lipid plot (black plot, Figure 10). During this steady phase after about 15 ns, the hydrophobic part of the signal peptide is penetrating deeper into the lipid layer (Figure 11). There, the clearly visible interaction contact between the protein model and the lipid layer after 50 ns of MD simulation is shown.

Bottom Line: In this work, computational chemistry and molecular-biological methods were combined to localize and characterize SP-G.With the help of a protein structure model, specific antibodies were obtained which allowed the detection of SP-G not only on mRNA but also on protein level.This includes also the possibility of interactions with lipid systems and with that, a potential surface-regulatory feature of SP-G.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Halle, Germany.

ABSTRACT
Surfactant proteins (SP) are well known from human lung. These proteins assist the formation of a monolayer of surface-active phospholipids at the liquid-air interface of the alveolar lining, play a major role in lowering the surface tension of interfaces, and have functions in innate and adaptive immune defense. During recent years it became obvious that SPs are also part of other tissues and fluids such as tear fluid, gingiva, saliva, the nasolacrimal system, and kidney. Recently, a putative new surfactant protein (SFTA2 or SP-G) was identified, which has no sequence or structural identity to the already know surfactant proteins. In this work, computational chemistry and molecular-biological methods were combined to localize and characterize SP-G. With the help of a protein structure model, specific antibodies were obtained which allowed the detection of SP-G not only on mRNA but also on protein level. The localization of this protein in different human tissues, sequence based prediction tools for posttranslational modifications and molecular dynamic simulations reveal that SP-G has physicochemical properties similar to the already known surfactant proteins B and C. This includes also the possibility of interactions with lipid systems and with that, a potential surface-regulatory feature of SP-G. In conclusion, the results indicate SP-G as a new surfactant protein which represents an until now unknown surfactant protein class.

Show MeSH
Related in: MedlinePlus