Open AccessStructural model for an AxxxG‐mediated dimer of surfactant‐associated protein C
Author(s) -
Kairys Visvaldas,
Gilson Michael K.,
Luy Burkhard
Publication year - 2004
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.2004.04107.x
Subject(s) - glycophorin , pulmonary surfactant , dimer , chemistry , biophysics , peptide sequence , helix (gastropod) , stereochemistry , crystallography , biochemistry , biology , membrane , gene , ecology , organic chemistry , snail
The pulmonary surfactant prevents alveolar collapse and is required for normal pulmonary function. One of the important components of the surfactant besides phospholipids is surfactant‐associated protein C (SP‐C). SP‐C shows complex oligomerization behavior and a transition to β‐amyloid‐like fibril structures, which are not yet fully understood. Besides this nonspecific oligomerization, MS and chemical cross‐linking data combined with CD spectra provide evidence of a specific, mainly α‐helical, dimer at low to neutral pH. Furthermore, resistance to CNBr cleavage and dual NMR resonances of porcine and human recombinant SP‐C with Met32 replaced by isoleucine point to a dimerization site located at the C‐terminus of the hydrophobic α‐helix of SP‐C, where a strictly conserved heptapeptide sequence is found. Computational docking of two SP‐C helices, described here, reveals a dimer with a helix–helix interface that strikingly resembles that of glycophorin A and is mediated by an AxxxG motif similar to the experimentally determined GxxxG pattern of glycophorin A. It is highly likely that mature SP‐C adopts such a dimeric structure in the lamellar bilayer systems found in the surfactant. Dimerization has been shown in previous studies to have a role in sorting and trafficking of SP‐C and may also be important to the surfactant function of this protein.