The role of charged amphipathic helices in the structure and function of surfactant protein B

  1. A.J. Waring,
  2. F.J. Walther,
  3. L.M. Gordon,
  4. J.M. Hernandez-Juviel,
  5. T. Hong,
  6. M.A. Sherman,
  7. C. Alonso,
  8. T. Alig,
  9. A. Braun,
  10. D. Bacon,
  11. J.A. Zasadzinski

Article first published online: 7 OCT 2005

DOI: 10.1111/j.1399-3011.2005.00300.x

Issue

The Journal of Peptide Research

The Journal of Peptide Research

Volume 66, Issue 6, pages 364–374, December 2005

Additional Information

How to Cite

Waring, A., Walther, F., Gordon, L., Hernandez-Juviel, J., Hong, T., Sherman, M., Alonso, C., Alig, T., Braun, A., Bacon, D. and Zasadzinski, J. (2005), The role of charged amphipathic helices in the structure and function of surfactant protein B. The Journal of Peptide Research, 66: 364–374. doi: 10.1111/j.1399-3011.2005.00300.x

Author Information

  1. A. J. Waring, Department of Medicine, UCLA, Los Angeles, CA 90095 and Los Angeles Biomedical Research Institute, Torrance, CA 90502, USA F. J. Walther, L. M. Gordon and J. M. Hernandez-Juviel, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA T. Hong, Department of Medicine, UCLA, Los Angeles, CA 90095, USA M. A. Sherman, Department of Biomedical Informatics, City of Hope National Medical Center, Duarte, CA 91010, USA C. Alonso, T. Alig, A. Braun, D. Bacon and J. A. Zasadzinski, Departments of Chemical Engineering and Materials, University of California, Santa Barbara, CA 93106, USA

*A.J. Waring Department of Medicine Division of Infectious Diseases UCLA School of Medicine Center for Health Sciences CHS-37-055,10833, Le Conte Avenue Los Angeles,CA 90095, USA. Tel.: (310) 794-7228 Fax: (310) 206-8766 E-mail: awaring@ucla.edu

Publication History

  1. Issue published online: 4 DEC 2008
  2. Article first published online: 7 OCT 2005
  3. Dates: Received 3 May 2005 Revised 25 July 2005 Accepted 20 August 2005

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Keywords:

  • amphipathic helices;
  • captive bubble surfactometry;
  • isotope-enhanced Fourier transform infrared spectroscopy;
  • peptide;
  • saposin;
  • secondary structure;
  • surfactant activity

Abstract:  Surfactant protein B (SP-B) is essential for normal lung surfactant function. Theoretical models predict that the disulfide cross-linked, N- and C-terminal domains of SP-B fold as charged amphipathic helices, and suggest that these adjacent helices participate in critical surfactant activities. This hypothesis is tested using a disulfide-linked construct (Mini-B) based on the primary sequences of the N- and C-terminal domains. Consistent with theoretical predictions of the full-length protein, both isotope-enhanced Fourier transform infrared (FTIR) spectroscopy and molecular modeling confirm the presence of charged amphipathic α-helices in Mini-B. Similar to that observed with native SP-B, Mini-B in model surfactant lipid mixtures exhibits marked in vitro activity, with spread films showing near-zero minimum surface tensions during cycling using captive bubble surfactometry. In vivo, Mini-B shows oxygenation and dynamic compliance that compare favorably with that of full-length SP-B. Mini-B variants (i.e. reduced disulfides or cationic residues replaced by uncharged residues) or Mini-B fragments (i.e. unlinked N- and C-terminal domains) produced greatly attenuated in vivo and in vitro surfactant properties. Hence, the combination of structure and charge for the amphipathic α-helical N- and C-terminal domains are key to SP-B function.

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