Structure-Function Relationships of Surfactant Proteins SP-B and SP-C

Waring, AJ; Fan, Botao; Nguyen, Thuy Trang M.; Amirkhanian, J. D.; Taeusch, William

doi:10.1159/000417852

Cited by 11 publications

(13 citation statements)

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“…The standard lipid mixture contained dipalmitoyl phosphatidylcholine (DPPC), egg phosphatidyl glycerol (PG), and palmitic acid (PA), 68:22:9 (wt/wt). These lipids have been employed in several reconstitution studies and are referred to as Tanaka lipids (9,17,26 Spectocopy and Fourier Transform Infared (FIR) Spectroscopy. CD spectroscopy was performed on Jasco (Easton, MD) J600 or J720 spectropolarimeters.…”

Section: Methodsmentioning

confidence: 99%

“…The standard lipid mixture contained dipalmitoyl phosphatidylcholine (DPPC), egg phosphatidyl glycerol (PG), and palmitic acid (PA), 68:22:9 (wt/wt). These lipids have been employed in several reconstitution studies and are referred to as Tanaka lipids (9,17,26 an aqueous solution of (+)-10-camphorsulfonic acid (1 mg/ ml) in a 1-mm path length cell (27). Samples were scanned from 250 nm to 195 nm, scan rate of 10 nm per minute.…”

Section: Methodsmentioning

confidence: 99%

“…Negatively and positively charged residues are found at the carboxyl terminus (one aspartate, one glutamate, four arginines). Intra-and intermolecular sulfhydryl bonds are important structural features of the mature protein, which contains seven cysteines and is oligomeric under oxidizing conditions (9,10).…”

mentioning

confidence: 99%

“…Quantitative measurements of the amphipathicity of the human amino acid sequence of SP-B using the Eisenberg hydrophobic algorithm (20) predict that the amino-terminal sequence has a high a hydrophobic moment (9,21). Therefore, we investigated the amino-terminal sequence of SP-B to identify secondary structures and specific conformations associated with surface activity in peptide/lipid dispersions.…”

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confidence: 99%

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Surfactant protein B: lipid interactions of synthetic peptides representing the amino-terminal amphipathic domain.

Bruni

Taeusch

Waring

1991

Proc. Natl. Acad. Sci. U.S.A.

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The mechanisms by which pulmonary surfactant protein B (SP-B) affects the surface activity of surfactant lipids are unclear. We have studied the peptide/lipid interactions of the amino-terminal amphipathic domain of SP-B by comparing the secondary conformations and surface activities of a family of synthetic peptides based on the native human SP-B sequence, modified by site-specific amino acid substitutions. Circular dichroism measurements show an ahelical structure correlating with the ability of the peptides to interact with lipids and with the surface activity of peptide/lipid dispersions. Amino acid substitutions altering either the charge or the hydrophobicity of the residues lowered the helical content and reduced the association of the aminoterminal segment with lipid dispersions. Surface activity of peptide/lipid mixtures was maximally altered by reversal of charge in synthetic peptides. These observations indicate that electrostatic interactions and hydrophobicity are important factors in determining optimal structure and function of surfactant peptides in lipid dispersions.Surfactant protein B (SP-B, Mr 9000; refs. 1 and 2) is encoded on chromosome 2 and synthesized by type 2 pneumocytes (3-6). The primary translation product for SP-B is a 381-residue glycosylated preprotein (Mr 42,000) (7). Amino-and carboxyl-terminal proteolytic cleavage produces a 79-residue peptide, with amino terminus located at residue 201 of the preprotein. Mature SP-B lacks glycosylation sites, is highly hydrophobic, and has a basic pl. In contrast to surfactant protein C (SP-C), SP-B has no covalently linked lipids, although it coisolates with SP-C and surfactant lipids (8). Four of 10 positively charged residues (two arginines, two lysines) appear at the amino terminus. Negatively and positively charged residues are found at the carboxyl terminus (one aspartate, one glutamate, four arginines). Intra-and intermolecular sulfhydryl bonds are important structural features of the mature protein, which contains seven cysteines and is oligomeric under oxidizing conditions (9, 10).Together with surfactant protein A (SP-A) and SP-C, SP-B interacts with lipids to form mammalian pulmonary surfactant. SP-B is present in lamellar bodies in type II pneumocytes and appears in bronchoalveolar lavage. SP-B from bovine and porcine sources contributes to the function of surfactant preparations used in replacement therapies (11)(12)(13)(14)(15). Synthetic SP-B (16) and synthetic peptides from predicted amphipathic sequences of human SP-B (17) emulate native SP-B in surfactant lipid dispersions (13,(16)(17)(18)(19).Quantitative measurements of the amphipathicity of the human amino acid sequence of SP-B using the Eisenberg hydrophobic algorithm (20) predict that the amino-terminal sequence has a high a hydrophobic moment (9, 21). Therefore, we investigated the amino-terminal sequence of SP-B to identify secondary structures and specific conformations associated with surface activity in peptide/lipid dispersions.Based on the native amino-te...

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Section: Methodsmentioning

confidence: 99%

“…The standard lipid mixture contained dipalmitoyl phosphatidylcholine (DPPC), egg phosphatidyl glycerol (PG), and palmitic acid (PA), 68:22:9 (wt/wt). These lipids have been employed in several reconstitution studies and are referred to as Tanaka lipids (9,17,26 an aqueous solution of (+)-10-camphorsulfonic acid (1 mg/ ml) in a 1-mm path length cell (27). Samples were scanned from 250 nm to 195 nm, scan rate of 10 nm per minute.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Surfactant protein B: lipid interactions of synthetic peptides representing the amino-terminal amphipathic domain.

Bruni

Taeusch

Waring

1991

Proc. Natl. Acad. Sci. U.S.A.

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“…Logically, the design, synthesis, and characterization of simpler peptide mimics (KL 4 )21 or shorter SP-B fragments (SP-B 1-25 , SP-B 53-78 )22–26 have been explored. The latter terminal, surface-active segments are connected via two proximally close disulfide bonds in natural SP-B.…”

Section: Introductionmentioning

confidence: 99%

Close mimicry of lung surfactant protein B by “clicked” dimers of helical, cationic peptoids

et al. 2009

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A family of peptoid dimers developed to mimic SP-B is presented, where two amphipathic, cationic helices are linked by an achiral octameric chain. SP-B is a vital therapeutic protein in lung surfactant replacement therapy, but its large-scale isolation or chemical synthesis is impractical. Enhanced biomimicry of SP-B’s disulfide-bonded structure has been previously attempted via disulfide-mediated dimerization of SP-B1-25 and other peptide mimics, which improved surface activity relative to the monomers. Herein, the effects of disulfide- or ‘click’-mediated (1,3-dipolar cycloaddition) dimerization, as well as linker chemistry, on the lipid-associated surfactant activity of a peptoid monomer are described. Results revealed that the ‘clicked’ peptoid dimer enhanced in vitro surface activity in a DPPC:POPG:PA lipid film relative to its disulfide-bonded and monomeric counterparts in both surface balance and pulsating bubble surfactometry studies. On the pulsating bubble surfactometer, the film containing the ‘clicked’ peptoid dimer outperformed all presented peptoid monomers and dimers, and two SP-B derived peptides, attaining an adsorbed surface tension of 22 mN m−1, and maximum and minimum cycling values of 42 mN m−1 and near-zero, respectively.

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Synthetic Mimics of Surfactant Proteins B and C:In VitroSurface Activity and Effects on Lung Compliance in Two Animal Models of Surfactant Deficiency

Bruni

Hernández-Juviel

Tanoviceanu

et al. 1998

Molecular Genetics and Metabolism

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Structure-Function Relationships of Surfactant Proteins SP-B and SP-C

Cited by 11 publications

References 0 publications

Surfactant protein B: lipid interactions of synthetic peptides representing the amino-terminal amphipathic domain.

Surfactant protein B: lipid interactions of synthetic peptides representing the amino-terminal amphipathic domain.

Close mimicry of lung surfactant protein B by “clicked” dimers of helical, cationic peptoids

Synthetic Mimics of Surfactant Proteins B and C:In VitroSurface Activity and Effects on Lung Compliance in Two Animal Models of Surfactant Deficiency

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