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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

PROSA plot for the obtained SP-G structure model.The combined pair and surface potential is plotted versus the sequence position. The completely negative curve and the overall Z-score of −6.16 suggest a native-like fold.
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pone-0047789-g002: PROSA plot for the obtained SP-G structure model.The combined pair and surface potential is plotted versus the sequence position. The completely negative curve and the overall Z-score of −6.16 suggest a native-like fold.

Mentions: The full length protein sequence (including the N-terminal 19 amino acid signal peptide) was used for the protein model generation because there are no data available which indicate in which form SP-G is present at its site of action. First attempts to obtain the 3D structure by homology modeling failed because there were no entries in the PDB with a sufficiently high sequence homology to SP-G. Also the threading method did not lead to satisfying results since the sequence of SP-G contains no conserved domains and the secondary structure prediction for a sequence with only 78 amino acids is very complicated. Therefore, the sequence was submitted to the online server Robetta. It applies ab initio folding to obtain a structural model in a very time consuming process. But for the short SP-G sequence, results were expected in reasonable time. Indeed, the obtained model showed a very promising quality and needed only minor optimizations. After energy minimization and MD refinement in YASARA, the PROCHECK evaluation shows a very good stereochemical quality of the protein model. From the 78 amino acids, 95.5% are in the most favored regions, the remaining 4.5% show dihedral angle values in the additional allowed regions of the Ramachandran plot. The evaluation with PROSA shows a very good model quality as well. The plot of the combined pair and surface potential (Figure 2) is clearly negative for all regions of the protein and the combined Z-score of -6.16 is close to the average value (−7.77) for proteins of this length. These validation results indicate a good native-like fold of the protein structure model.


"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)

PROSA plot for the obtained SP-G structure model.The combined pair and surface potential is plotted versus the sequence position. The completely negative curve and the overall Z-score of −6.16 suggest a native-like fold.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0047789-g002: PROSA plot for the obtained SP-G structure model.The combined pair and surface potential is plotted versus the sequence position. The completely negative curve and the overall Z-score of −6.16 suggest a native-like fold.
Mentions: The full length protein sequence (including the N-terminal 19 amino acid signal peptide) was used for the protein model generation because there are no data available which indicate in which form SP-G is present at its site of action. First attempts to obtain the 3D structure by homology modeling failed because there were no entries in the PDB with a sufficiently high sequence homology to SP-G. Also the threading method did not lead to satisfying results since the sequence of SP-G contains no conserved domains and the secondary structure prediction for a sequence with only 78 amino acids is very complicated. Therefore, the sequence was submitted to the online server Robetta. It applies ab initio folding to obtain a structural model in a very time consuming process. But for the short SP-G sequence, results were expected in reasonable time. Indeed, the obtained model showed a very promising quality and needed only minor optimizations. After energy minimization and MD refinement in YASARA, the PROCHECK evaluation shows a very good stereochemical quality of the protein model. From the 78 amino acids, 95.5% are in the most favored regions, the remaining 4.5% show dihedral angle values in the additional allowed regions of the Ramachandran plot. The evaluation with PROSA shows a very good model quality as well. The plot of the combined pair and surface potential (Figure 2) is clearly negative for all regions of the protein and the combined Z-score of -6.16 is close to the average value (−7.77) for proteins of this length. These validation results indicate a good native-like fold of the protein structure model.

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