title: Structural model for an AxxxG-mediated dimer of surfactant-associated protein C.
abstract: 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 beta-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 alpha-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 alpha-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.
authors.affiliation: Center for Advanced Research in Biotechnology, 9600 Gudelsky Drive, Rockville, MD 20850, USA.
authors.forename: Visvaldas
authors.initials: V
authors.lastname: Kairys
authors.forename: Michael K
authors.initials: MK
authors.lastname: Gilson
authors.forename: Burkhard
authors.initials: B
authors.lastname: Luy
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D019295:Computational Biology; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D037721:Pulmonary Surfactant-Associated Protein C / Q000737:chemistry* / Q000378:metabolism
chemical_list: D037721:Pulmonary Surfactant-Associated Protein C