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

A. J. Waring, F. J. Walther, L. M. Gordon, J. M. Hernandez-Juviel, T. Hong, M. A. Sherman, C. Alonso, T. Alig, A. Braun, D. Bacon, J. A. Zasadzinski

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58 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)364-374
Number of pages11
JournalJournal of Peptide Research
Issue number6
StatePublished - Dec 2005


  • Amphipathic helices
  • Captive bubble surfactometry
  • Isotope-enhanced Fourier transform infrared spectroscopy
  • Peptide
  • Saposin
  • Secondary structure
  • Surfactant activity

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