Interactions of the C-terminus of lung surfactant protein B with lipid bilayers are modulated by acyl chain saturation |
| |
Authors: | Vijay C Antharam Anna Kuznetsova Frank D Mills Edward Sternin |
| |
Institution: | a Department of Biochemistry and Molecular Biology and McKnight Brain Institute, Box 100245, Gainesville, FL 32610-0245, USA b Department of Physics, Brock University, St. Catharines, Ontario Canada L2S 3A1 |
| |
Abstract: | Lung surfactant protein B (SP-B) is critical to minimizing surface tension in the alveoli. The C-terminus of SP-B, residues 59-80, has much of the surface activity of the full protein and serves as a template for the development of synthetic surfactant replacements. The molecular mechanisms responsible for its ability to restore lung compliance were investigated with circular dichroism, differential scanning calorimetry, and 31P and 2H solid-state NMR spectroscopy. SP-B59-80 forms an amphipathic helix which alters lipid organization and acyl chain dynamics in fluid lamellar phase 4:1 DPPC:POPG and 3:1 POPC:POPG MLVs. At higher levels of SP-B59-80 in the POPC:POPG lipid system a transition to a nonlamellar phase is observed while DPPC:POPG mixtures remain in a lamellar phase. Deuterium NMR shows an increase in acyl chain order in DPPC:POPG MLVs on addition of SP-B59-80; in POPC:POPG MLVs, acyl chain order parameters decrease. Our results indicate SP-B59-80 penetrates deeply into DPPC:POPG bilayers and binds more peripherally to POPC:POPG bilayers. Similar behavior has been observed for KL4, a peptide mimetic of SP-B which was originally designed using SP-B59-80 as a template and has been clinically demonstrated to be successful in treating respiratory distress syndrome. The ability of these helical peptides to differentially partition into lipid lamellae based on their degree of monounsaturation and subsequent changes in lipid dynamics suggest a mechanism for lipid organization and trafficking within the dynamic lung environment. |
| |
Keywords: | SP-B surfactant protein B NMR nuclear magnetic resonance CSA chemical shift anisotropy CD circular dichroism DSC differential scanning calorimetry MLV multilamellar vesicle LUV large unilamellar vesicle Lα fluid lamellar phase Lβ gel lamellar phase POPC 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine POPC-d31 1-d31-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine POPG 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol DPPC 1 2-dipalmitoyl-sn-Glycero-3-Phosphocholine DPPC-d62 1 2-d62-dipalmitoyl-sn-Glycero-3-Phosphocholine P/L peptide/lipid molar ratio HII inverted hexagonal phase |
本文献已被 ScienceDirect 等数据库收录! |
|