Pulmonary surfactant‐associated polypeptide C in a mixed organic solvent transforms from a monomeric α‐helical state into insoluble β‐sheet aggregates

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Abstract
In the 35‐residue pulmonary surfactant‐associated lipopolypeptide C (SP‐C), the stability of the valyl‐rich α‐helix comprising residues 9–34 has been monitored by circular dichroism, nuclear magnetic resonance, and Fourier transform infrared spectroscopy in both a mixed organic solvent and in phospholipid micelles. The α‐helical form of SP‐C observed in freshly prepared solutions in a mixed solvent of CHCl3/CH3OH/0.1 M HCl 32:64:5 (v/v/v) at 10°C undergoes within a few days an irreversible transformation to an insoluble aggregate that contains β‐sheet secondary structure. Hydrogen exchange experiments revealed that this conformational transition proceeds through a transition state with an Eyring free activation enthalpy of about 100 kJ mol–1, in which the polypeptide segment 9–27 largely retains a helical conformation. In dodecylphosphocholine micelles, the helical form of SP‐C was maintained after seven weeks at 50 °C. The α‐helical form of SP‐C thus seems to be the thermodynamically most stable state in this micellar environment, whereas its presence in freshly prepared samples in the aforementioned mixed solvent is due to a high kinetic barrier for unfolding. These observations support a previously proposed pathway for in vivo synthesis of SP‐C through proteolytic processing from a 21‐kDa precursor protein.