A unique sugar-binding site mediates the distinct anti-influenza activity of pig surfactant protein D

Martin Van Eijk, Michael J. Rynkiewicz, Mitchell R. White, Kevan L. Hartshorn, Xueqing Zou, Klaus Schulten, Dong Luo, Erika C. Crouch, Tanya R. Cafarella, James F. Head, Henk P. Haagsman, Barbara A. Seaton

Research output: Contribution to journalArticle

Abstract

Pigs can act as intermediate hosts by which reassorted influenza A virus (IAV) strains can be transmitted to humans and cause pandemic influenza outbreaks. The innate host defense component surfactant protein D (SP-D) interacts with glycans on the hemagglutinin of IAV and contributes to protection against IAV infection in mammals. This study shows that a recombinant trimeric neck lectin fragment derived from porcine SP-D (pSP-D) exhibits profound inhibitory activity against IAV, in contrast to comparable fragments derived from human SP-D. Crystallographic analysis of the pSP-D fragment complexed with a viral sugar component shows that a unique tripeptide loop alters the lectin site conformation of pSP-D. Molecular dynamics simulations highlight the role of this flexible loop, which adopts a more stable conformation upon sugar binding and may facilitate binding to viral glycans through contact with distal portions of the branched mannoside. The combined data demonstrate that porcine-specific structural features of SP-D contribute significantly to its distinct anti-IAV activity. These findings could help explain why pigs serve as important reservoirs for newly emerging pathogenic IAV strains.

Original languageEnglish (US)
Pages (from-to)26666-26677
Number of pages12
JournalJournal of Biological Chemistry
Volume287
Issue number32
DOIs
StatePublished - Aug 3 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Van Eijk, M., Rynkiewicz, M. J., White, M. R., Hartshorn, K. L., Zou, X., Schulten, K., Luo, D., Crouch, E. C., Cafarella, T. R., Head, J. F., Haagsman, H. P., & Seaton, B. A. (2012). A unique sugar-binding site mediates the distinct anti-influenza activity of pig surfactant protein D. Journal of Biological Chemistry, 287(32), 26666-26677. https://doi.org/10.1074/jbc.M112.368571