Stability of an amphipathic helix-hairpin surfactant peptide in liposomes
Copyright © 2016 Elsevier B.V. All rights reserved..
Surfactant protein B (SP-B; 79 residues) is a member of the saposin superfamily and plays a pivotal role in lung function. The N- and C-terminal regions of SP-B, cross-linked by two disulfides, were theoretically predicted to fold as charged amphipathic helices, suggesting participation in surfactant activities. Previous studies with oxidized Super Mini-B (SMB), a construct based on the N- and C-regions of SP-B (i.e., residues 1-25 and 63-78) joined with a designer turn (-PKGG-) and two disulfides, indicated that freshly prepared SMB in lipids folded as a surface active, α-helix-hairpin. Because other peptides modeled on α-helical SP domains lost helicity and surfactant activity on storage, experiments were here performed on oxidized SMB in surfactant liposomes stored at ~2-8°C for ≤5.5years. Captive bubble surfactometry confirmed low minimum surface tensions for fresh and stored SMB preparations. FTIR spectroscopy of fresh and stored SMB formulations showed secondary structures compatible with the peptide folding as α-helix-hairpin. A homology (I-TASSER) model of oxidized SMB demonstrated a globular protein, exhibiting a core of hydrophobic residues and a surface of polar residues. Since mass spectroscopy indicated that the disulfides were maintained on storage, the stability of SMB may be partly due to the disulfides bringing the N- and C-α-helices closer. Mass spectroscopy of stored SMB preparations showed some methionine oxidation, and also partial deacylation of surfactant phospholipids to form lyso-derivatives. However, the stable conformation and activity of stored SMB surfactant suggest that the active helix-hairpin resists these chemical changes which otherwise may lead to surfactant inhibition.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1858 |
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| Enthalten in: |
Biochimica et biophysica acta - 1858(2016), 12 vom: 19. Dez., Seite 3113-3119 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Waring, Alan J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.10.2017 Date Revised 13.11.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbamem.2016.09.014 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Stability of an amphipathic helix-hairpin surfactant peptide in liposomes |
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| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2016 Elsevier B.V. All rights reserved. | ||
| 520 | |a Surfactant protein B (SP-B; 79 residues) is a member of the saposin superfamily and plays a pivotal role in lung function. The N- and C-terminal regions of SP-B, cross-linked by two disulfides, were theoretically predicted to fold as charged amphipathic helices, suggesting participation in surfactant activities. Previous studies with oxidized Super Mini-B (SMB), a construct based on the N- and C-regions of SP-B (i.e., residues 1-25 and 63-78) joined with a designer turn (-PKGG-) and two disulfides, indicated that freshly prepared SMB in lipids folded as a surface active, α-helix-hairpin. Because other peptides modeled on α-helical SP domains lost helicity and surfactant activity on storage, experiments were here performed on oxidized SMB in surfactant liposomes stored at ~2-8°C for ≤5.5years. Captive bubble surfactometry confirmed low minimum surface tensions for fresh and stored SMB preparations. FTIR spectroscopy of fresh and stored SMB formulations showed secondary structures compatible with the peptide folding as α-helix-hairpin. A homology (I-TASSER) model of oxidized SMB demonstrated a globular protein, exhibiting a core of hydrophobic residues and a surface of polar residues. Since mass spectroscopy indicated that the disulfides were maintained on storage, the stability of SMB may be partly due to the disulfides bringing the N- and C-α-helices closer. Mass spectroscopy of stored SMB preparations showed some methionine oxidation, and also partial deacylation of surfactant phospholipids to form lyso-derivatives. However, the stable conformation and activity of stored SMB surfactant suggest that the active helix-hairpin resists these chemical changes which otherwise may lead to surfactant inhibition | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Captive bubble surfactometry | |
| 650 | 4 | |a FTIR spectroscopy | |
| 650 | 4 | |a Homology modeling | |
| 650 | 4 | |a Lyso-phospholipids | |
| 650 | 4 | |a Super Mini-B (SMB) | |
| 650 | 4 | |a Surfactant lipids | |
| 650 | 4 | |a Surfactant protein B (SP-B) | |
| 650 | 7 | |a Disulfides |2 NLM | |
| 650 | 7 | |a Lipids |2 NLM | |
| 650 | 7 | |a Liposomes |2 NLM | |
| 650 | 7 | |a Pulmonary Surfactant-Associated Protein B |2 NLM | |
| 700 | 1 | |a Gupta, Monik |e verfasserin |4 aut | |
| 700 | 1 | |a Gordon, Larry M |e verfasserin |4 aut | |
| 700 | 1 | |a Fujii, Gary |e verfasserin |4 aut | |
| 700 | 1 | |a Walther, Frans J |e verfasserin |4 aut | |
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