tailieunhanh - Báo cáo khoa học: Structural model for an AxxxG-mediated dimer of surfactant-associated protein C

The pulmonary surfactant prevents alveolar collapse and is required for normal pulmonary function. One of the important components of the surfactant besides phos-pholipids is surfactant-associated protein C (SP-C). SP-C shows complex oligomerization behavior and a transition to b-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, mainlya-helical, dimer at lowto neutral pH | Eur. J. Biochem. 271 2086-2092 2004 FEBS 2004 doi Structural model for an AxxxG-mediated dimer of surfactant-associated protein C Visvaldas Kairys1 Michael K. Gilson1 and Burkhard Luy2 1Center for Advanced Research in Biotechnology Rockville MD USA 2Institut fur Organische Chemie und Biochemie der Technischen Universitdt Miinchen Germany 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 b-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 a-helical dimer at low to neutral pH. furthermore sesiatrince to CNBr cleavage and dual CMR 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 a-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. Keywords dimerization docking surfactant-associated protein C SP-C . The liquid-air interface in the alveoli of mammalian lungs is coated with a surfactant monolayer that reduces surface tension and thus opposes collapse of the alveoli 1 . The surfactant is composed