Cation-mediated conformational variants of surfactant protein A

Surfactant protein A (SP-A) is the major protein of pulmonary surfactant. T his protein is implicated in regulating surfactant secretion, alveolar proc essing, recycling, and in non-serum-induced immune response. An increasing body of work indicates the importance of cations, particularly calcium, on SP-A function. However, little information exists on the effects of cations on SP-A quaternary structure. Here, the quaternary organisation of bovine surfactant protein A in the presence of cations has been quantitatively and systematically studied by transmission electron microscopy. The conformati on of SP-A is altered by the presence of cations, especially calcium, then sodium, and to a small extent, magnesium. There is a transition concentrati on, unique for each cation, at which a conformational switch occurs. These transition concentrations are. 5 mM for CaCl2, 100 mM for NaCl and 1 mM for MgCl2. Below these concentrations, SP-A exists primarily in an opened form with a large head diameter of 20 nm; above it, SP-A is mostly in a closed form due to a compaction of the headgroups resulting in a head diameter of 11 nm. There is a corresponding increase in particle length from 17 nm for opened SP-A to 20 nm for closed SP-A. The fact that the transition concentr ations are within physiological range suggests that cation-mediated conform ational changes of SP-A could be operative in vivo. (C) 1999 Elsevier Scien ce B.V. All rights reserved.