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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

Posttranslationally modified SP-G model with DPPC monolayer after 50 ns MD simulation.The lipids are shown with a yellow, the posttranslational modifications at position 37, 62, 70, 76, and 78 are shown with a red van der Waals surface to illustrate the tight interactions. Furthermore, the protein backbone is shown with the ribbon presentation (α-helices: blue; β-sheets: red, coil: cyan).
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pone-0047789-g012: Posttranslationally modified SP-G model with DPPC monolayer after 50 ns MD simulation.The lipids are shown with a yellow, the posttranslational modifications at position 37, 62, 70, 76, and 78 are shown with a red van der Waals surface to illustrate the tight interactions. Furthermore, the protein backbone is shown with the ribbon presentation (α-helices: blue; β-sheets: red, coil: cyan).

Mentions: Simulations with the same conditions were started for the SP-G model carrying posttranslational modifications as well. But in this case, a totally different interaction site between protein and lipids was obtained. First calculations indicated that the attached palmitoylation could interact with the lipid surface. For this reason, a simulation was started where the palmitoyl chain was already interacting with the monolayer at the beginning. After 50 ns MD simulation, the resulting protein-monolayer complex was analyzed (Figure 12). The α-helix 42–56 is on the surface of the complex, interacting with the solvent and not with the lipid surface as for the unmodified model. Instead, the palmitoylation on Cys76 and the protein part ranging from position 15 to 30 are interacting considerably with the lipids, the latter even immersing deep into the monolayer. The α-helical character of the signal peptide is maintained over the whole simulation. It is covering the hydrophobic protein core and is nicely stabilized in this conformation. The position of the whole protein on the lipid surface is fixed on three points by the attached glycosylations, which can interact significantly with the lipid head groups and act like anchors. This is also the reason why the protein RMSD plot for this simulation (red plot, Figure 9) is very stable. However, this strong interaction and the deep immersion of the protein into the lipid system affect the monolayer behavior. As for example, the area per lipid (red plot, Figure 10) is still essentially stable, but on average significantly lower than for the protein model without modifications.


"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)

Posttranslationally modified SP-G model with DPPC monolayer after 50 ns MD simulation.The lipids are shown with a yellow, the posttranslational modifications at position 37, 62, 70, 76, and 78 are shown with a red van der Waals surface to illustrate the tight interactions. Furthermore, the protein backbone is shown with the ribbon presentation (α-helices: blue; β-sheets: red, coil: cyan).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0047789-g012: Posttranslationally modified SP-G model with DPPC monolayer after 50 ns MD simulation.The lipids are shown with a yellow, the posttranslational modifications at position 37, 62, 70, 76, and 78 are shown with a red van der Waals surface to illustrate the tight interactions. Furthermore, the protein backbone is shown with the ribbon presentation (α-helices: blue; β-sheets: red, coil: cyan).
Mentions: Simulations with the same conditions were started for the SP-G model carrying posttranslational modifications as well. But in this case, a totally different interaction site between protein and lipids was obtained. First calculations indicated that the attached palmitoylation could interact with the lipid surface. For this reason, a simulation was started where the palmitoyl chain was already interacting with the monolayer at the beginning. After 50 ns MD simulation, the resulting protein-monolayer complex was analyzed (Figure 12). The α-helix 42–56 is on the surface of the complex, interacting with the solvent and not with the lipid surface as for the unmodified model. Instead, the palmitoylation on Cys76 and the protein part ranging from position 15 to 30 are interacting considerably with the lipids, the latter even immersing deep into the monolayer. The α-helical character of the signal peptide is maintained over the whole simulation. It is covering the hydrophobic protein core and is nicely stabilized in this conformation. The position of the whole protein on the lipid surface is fixed on three points by the attached glycosylations, which can interact significantly with the lipid head groups and act like anchors. This is also the reason why the protein RMSD plot for this simulation (red plot, Figure 9) is very stable. However, this strong interaction and the deep immersion of the protein into the lipid system affect the monolayer behavior. As for example, the area per lipid (red plot, Figure 10) is still essentially stable, but on average significantly lower than for the protein model without modifications.

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