COLL 373 |
| Alan J. Waring1, Larry M. Gordon2, Frans J. Walther2, Jose M. Hernandez-Juviel1, Mark A. Sherman3, Coralie Alonso4, and Joseph A. Zasadzinski5. (1) Research and Education Institute, Bldg. F5 South, Research and Education Institute at Harbor-UCLA, 1124 West Carson Street, Torrance, CA 90502, (2) Research and Education Institute, Bldg. F5 South, Reseach and Education Institute at Harbor-UCLA, 1124 West Carson Street, Torrance, CA 90502, (3) Division of Information Sciences, Beckman Resarch Institute, City of Hope Medical Center, City of Hope Medical Center, Duarte, CA 91010, (4) Department of Chemical Engineering, University of California Santa Barbara, Engineering II, Santa Barbara, CA 93106, (5) Department of Chemical Engineering, University of Califirnia, Santa Barbara, Santa Barbara, CA 93106-5080 |
| Surfactant protein B (SP-B) is a small (MW~8700 da), lipid-associating protein that belongs to the Saposin protein family. SP-B is found in the mammalian lung and is a critical component for normal lung function. The mature protein has a dominant amphipathic, alpha-helical conformation with most of its cationic residues localized in the disulfide linked N-terminal and C-terminal regions. These cationic amphipathic helical domains may provide an important surface for interactions with anionic lung surfactant lipid. Here, we have studied the structure of the C-terminal segment (SP-B residues 63-78) by determining residue-specific conformations using isotope-enhanced Fourier transform infrared (FTIR) spectroscopy. Combining the 13C-enhanced FTIR results with molecular simulations indicate that the C-terminal segment may assume helical conformations similar to those observed for the homologous C-terminal regions of other Saposin-folding proteins. In vitro measurements of the C-terminal peptide in surfactant lipid films suggest that this segment captures many of the surface activities of full-length SP-B. In vivo studies of the peptide in simulated surfactant lipids show moderate improvements in oxygenation and lung compliance, suggesting that this domain may be an important element in the parent proteins’ functioning in the lung. Supported by NIH RO1 HL55534, HL51177 and UC Tobacco Related Disease Research Program gant 8RT-0077. |
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Surface and Colloid Chemistry Award Symposium Honoring Joseph Zasadzinski
8:10 AM-12:10 PM, Wednesday, March 31, 2004 Marriott -- Orange County 3, Oral
Division of Colloid and Surface Chemistry |