Size and structure of the hydrophobic low molecular weight surfactant-associated polypeptide

Abstract

The most abundant low molecular weight protein of pulmonary surfactant has unusual properties. Its primary structure has now been determined by analysis at the protein level. The highly hydrophobic polypeptide is resistant to cleavage with proteolytic enzymes, but it was possible to generate fragments by limited cleavage with concentrated HCl or with sodium in liquid ammonia. Acid hydrolysis of the peptide required exceptional conditions for release of all residues. The N-terminus is heterogeneous, and in its longest form the primary structure consists of 35 residues. This analysis establishes that the size of the major native hydrophobic surfactant polypeptide is considerably smaller than previously proposed. Biological effects of the polypeptide recombined with phospholipids are confirmed in vitro by using a pulsating bubble system and in vivo by using premature newborn rabbits. The molecule has branched-chain amino acid residues at about two-thirds of all positions and lacks nine types of residue. The middle third is composed entirely of hydrophobic residues, and fragments from this part are sparingly soluble even in organic solvents. The hydrophobic region is preceded by a more hydrophilic, N-terminal segment. Thus, the molecule has two contrasting parts, like a detergent, which may explain its essential role in the pulmonary surfactant system.