Pulmonary surfactant protein B: a structural model and a functional analogue

Area of Science:

• Biochemistry
• Structural Biology
• Pulmonary Medicine

Background:

• Pulmonary surfactant contains surfactant proteins B and C (SP-B, SP-C) and phospholipids, crucial for respiratory distress syndrome (RDS) treatment.
• SP-B, a hydrophobic, disulfide-linked dimer, is part of the saposin family but its function remains unclear.
• Understanding SP-B's structure and function is key to developing improved RDS therapies.

Purpose of the Study:

• To model the three-dimensional structure of SP-B.
• To elucidate the mechanism of action of SP-B.
• To identify potential SP-B analogues for synthetic surfactant development.

Main Methods:

• Generated a structural model of an SP-B subunit based on NK-lysin NMR data.
• Constructed the SP-B dimer model using its disulfide bond.
• Performed energy minimization to identify intersubunit interactions.
• Compared in vitro surface activity of SP-B containing mixtures with those using polymyxin B.

Main Results:

• The SP-B model revealed conserved residues (Glu51, Arg52) forming hydrogen bonds/ion pairs.
• These interactions create a central non-polar region flanked by positive charges, supporting lipid membrane cross-linking.
• Synthetic mixtures with polymyxin B showed surface activity comparable to SP-B mixtures, despite structural differences.

Conclusions:

• The structural model of SP-B supports its role in cross-linking lipid membranes.
• Polymyxin B's functional similarity suggests a potential pathway for designing SP-B analogues.
• This research opens avenues for creating novel synthetic surfactants for RDS treatment.