Structure binding relationship of human surfactant protein D and various lipopolysaccharide inner core structures

Anika Reinhardt, Marko Wehle, Andreas Geissner, Erika C. Crouch, Yu Kang, You Yang, Chakkumkal Anish, Mark Santer, Peter H. Seeberger

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

As a major player of the innate immune system, surfactant protein D (SP-D) recognizes and promotes elimination of various pathogens such as Gram-negative bacteria. SP-D binds to L-glycero-D-manno-heptose (Hep), a constituent of the partially conserved lipopolysaccharide (LPS) inner core of many Gram-negative bacteria. Binding and affinity of trimeric human SP-D to Hep in distinct LPS inner core glycans differing in linkages and adjacent residues was elucidated using glycan array and surface plasmon resonance measurements that were compared to in silico interaction studies. The combination of in vitro assays using defined glycans and molecular docking and dynamic simulation approaches provides insights into the interaction of trimeric SP-D with those glycan ligands. Trimeric SP-D wildtype recognized larger LPS inner core oligosaccharides with slightly enhanced affinity than smaller compounds suggesting the involvement of stabilizing secondary interactions. A trimeric human SP-D mutant D324N + D325N + R343K resembling rat SP-D bound to various LPS inner core structures in a similar pattern as observed for the wildtype but with higher affinity. The selective mutation of SP-D promotes targeting of LPS inner core oligosaccharides on Gram-negative bacteria to develop novel therapeutic agents.

Original languageEnglish
Pages (from-to)387-395
Number of pages9
JournalJournal of Structural Biology
Volume195
Issue number3
DOIs
StatePublished - Sep 1 2016

Keywords

  • Carbohydrate recognition domain
  • D324N + D325N + R343K mutant
  • Glycan array
  • Glycan binding affinity
  • Gram-negative bacteria
  • Lipopolysaccharide inner core structure
  • Molecular docking
  • Molecular dynamics simulations
  • Surface plasmon resonance
  • Surfactant protein D
  • Synthetic glycans

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