Abstract
Breathing is enabled by lung surfactant, a mixture of proteins and lipids that forms a surface-active layer and reduces surface tension at the air-water interface in lungs. Surfactant protein B (SP-B) is an essential component of lung surfactant. In this study we probe the mechanism underlying the important functional contributions made by the N-terminal 7 residues of SP-B, a region sometimes called the “insertion sequence”. These studies employed a construct of SP-B, SP-B (1–25,63–78), also called Super Mini-B, which is a 41-residue peptide with internal disulfide bonds comprising the N-terminal 7-residue insertion sequence and the N- and C-terminal helices of SP-B. Circular dichroism, solution NMR, and solid state 2H NMR were used to study the structure of SP-B (1–25,63–78) and its interactions with phospholipid bilayers. Comparison of results for SP-B (8–25,63–78) and SP-B (1–25,63–78) demonstrates that the presence of the 7-residue insertion sequence induces substantial disorder near the centre of the lipid bilayer, but without a major disruption of the overall mechanical orientation of the bilayers. This observation suggests the insertion sequence is unlikely to penetrate deeply into the bilayer. The 7-residue insertion sequence substantially increases the solution NMR linewidths, most likely due to an increase in global dynamics.
Highlights
Lung surfactant is a complex of lipids and proteins that lines the air-water interface at the alveolar surface
To explore the role of the N-terminal 7 residues of Surfactant protein B (SP-B), we first used 2H NMR to examine the effect of surfactant proteins (SPs)-B (1–25,63–78) on mechanically oriented lipid bilayers composed of a mixture of zwitterionic and anionic phospholipids, POPC-d31/POPG (7:3) (Figure 1)
The order parameters, SCD, calculated from the splittings (Table 1) for the acyl chain positions just adjacent to the terminal methyl group decreased with the addition of 1 mol% SPB (1–25,63,78) by 18%, 20% and 17% for C15, C14, and C13, respectively
Summary
Lung surfactant is a complex of lipids and proteins that lines the air-water interface at the alveolar surface. It is essential for reducing surface tension and preventing alveolar collapse [1,2]. Deficiency or inactivation of lung surfactant leads to potentially lethal respiratory disorders such as neonatal respiratory distress syndrome (NRDS) in premature newborns [8,9,10] and acute respiratory distress syndrome (ARDS) in patients with severe injury or illness [11,12,13]. Surfactant replacement therapy has been quite successful in treating NRDS [14,15]. Efforts to use replacement surfactant to treat ARDS have not demonstrated improvements in mortality rates far [9,12]
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