title: Structure binding relationship of human surfactant protein D and various lipopolysaccharide inner core structures.
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.
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Reinhardt
authors.affiliation: Department of Theory and Biosystems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany.
authors.forename: Marko
authors.initials: M
authors.lastname: Wehle
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Geissner
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States.
authors.forename: Erika C
authors.initials: EC
authors.lastname: Crouch
authors.affiliation: Department of Theory and Biosystems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany.
authors.forename: You
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany.
authors.forename: Chakkumkal
authors.initials: C
authors.lastname: Anish
authors.affiliation: Department of Theory and Biosystems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany. Electronic address: mark.santer@mpikg.mpg.de.
authors.forename: Mark
authors.initials: M
authors.lastname: Santer
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany. Electronic address: peter.seeberger@mpikg.mpg.de.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeberger
mesh_terms: D019943:Amino Acid Substitution; D018360:Crystallography, X-Ray; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000737:chemistry*; D062105:Molecular Docking Simulation; D011485:Protein Binding; D037663:Pulmonary Surfactant-Associated Protein D / Q000737:chemistry*
chemical_list: D008070:Lipopolysaccharides; D037663:Pulmonary Surfactant-Associated Protein D
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