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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

General simulation box setup.Two distinct DPPC lipid monolayers enclose a water phase (illustrated by single water molecules in ball and stick representation) with their polar head groups. The orientation of the protein (secondary structure only representation) centered in this water phase varies at the simulation start. On the alkyl chain side, the monolayers are separated by a vacuum phase because of the applied periodic boundary conditions.
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pone-0047789-g001: General simulation box setup.Two distinct DPPC lipid monolayers enclose a water phase (illustrated by single water molecules in ball and stick representation) with their polar head groups. The orientation of the protein (secondary structure only representation) centered in this water phase varies at the simulation start. On the alkyl chain side, the monolayers are separated by a vacuum phase because of the applied periodic boundary conditions.

Mentions: The protein-lipid simulations were carried out with the GROMACS package version 4.5.4 [47], [48]. The united-atom G53a6 force field [49] was modified after Kukol [50] to produce reasonable data for a DPPC-lipid system. To allow the simulation of the modified protein models, the force field was extended by residues for phosphorylated serine, threonine and tyrosine, palmitoylated cysteine, serine or threonine residues which are O-glycosylated with GlcNAc or GalNAc and N-glycosylated asparagine. The residue for the N-glycosylation consists of a pentasaccaride core with two GlcNAc and three mannose moieties (- GlcNAc-GlcNAc-mannose-(mannose)2 ). Parameters for all these groups were taken from building blocks of the original G53a6 force field and in the case of the phosphorylated amino acids from the G43a1p force field [51]. The CELLmicrocosmos MembraneEditor 2.2 [52] was used to build the initial simulation system (Figure 1). It consists of two DPPC monolayers with 128 molecules each which are separated on the polar head group side by a water phase. On the side of the lipid alkyl chains the two layers are divided by a vacuum phase since periodic boundary conditions are applied in all three dimensions. For every simulation, one copy of the protein model was placed in different orientations in the water phase between the two lipid layers and was neutralized with Na+ or Cl- ions, if necessary. This resulted in systems with a total size of approximately 60.000 atoms.


"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)

General simulation box setup.Two distinct DPPC lipid monolayers enclose a water phase (illustrated by single water molecules in ball and stick representation) with their polar head groups. The orientation of the protein (secondary structure only representation) centered in this water phase varies at the simulation start. On the alkyl chain side, the monolayers are separated by a vacuum phase because of the applied periodic boundary conditions.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0047789-g001: General simulation box setup.Two distinct DPPC lipid monolayers enclose a water phase (illustrated by single water molecules in ball and stick representation) with their polar head groups. The orientation of the protein (secondary structure only representation) centered in this water phase varies at the simulation start. On the alkyl chain side, the monolayers are separated by a vacuum phase because of the applied periodic boundary conditions.
Mentions: The protein-lipid simulations were carried out with the GROMACS package version 4.5.4 [47], [48]. The united-atom G53a6 force field [49] was modified after Kukol [50] to produce reasonable data for a DPPC-lipid system. To allow the simulation of the modified protein models, the force field was extended by residues for phosphorylated serine, threonine and tyrosine, palmitoylated cysteine, serine or threonine residues which are O-glycosylated with GlcNAc or GalNAc and N-glycosylated asparagine. The residue for the N-glycosylation consists of a pentasaccaride core with two GlcNAc and three mannose moieties (- GlcNAc-GlcNAc-mannose-(mannose)2 ). Parameters for all these groups were taken from building blocks of the original G53a6 force field and in the case of the phosphorylated amino acids from the G43a1p force field [51]. The CELLmicrocosmos MembraneEditor 2.2 [52] was used to build the initial simulation system (Figure 1). It consists of two DPPC monolayers with 128 molecules each which are separated on the polar head group side by a water phase. On the side of the lipid alkyl chains the two layers are divided by a vacuum phase since periodic boundary conditions are applied in all three dimensions. For every simulation, one copy of the protein model was placed in different orientations in the water phase between the two lipid layers and was neutralized with Na+ or Cl- ions, if necessary. This resulted in systems with a total size of approximately 60.000 atoms.

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