TCB Publications - Abstract

Martin van Eijk, Michael J. Rynkiewicz, Mitchell R. White, Kevan L. Hartshorn, Xueqing Zou, Klaus Schulten, Dong Luo, Erika C. Crouch, Tanya M. Cafarella, James F. Head, Henk P. Haagsman, and Barbara A. Seaton. Unique sugar-binding site mediates the distinct anti-influenza activity of pig surfactant protein D. Journal of Biological Chemistry, 287:26666-26677, 2012. (PMC: 3411006)

EIJK2012 Pigs can act as intermediate hosts via 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. The present 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 to explain why pigs serve as important reservoirs for newly emerging pathogenic IAV strains.

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