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

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• 作者：Anika Reinhardt^a ; ^b ; Marko Wehle^d ; Andreas Geissner^a ; ^b ; Erika C. Crouch^c ; Yu Kang^d ; ¹ ; You Yang^a ; ³ ; Chakkumkal Anish^a ; ² ; Mark Santer^d ; ^{mark.santer@mpikg.mpg.de" class="auth_mail" title="E-mail the corresponding author} ; Peter H. Seeberger^a ; ^b ; ^{peter.seeberger@mpikg.mpg.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Surfactant protein D ; D324N  ; +  ; D325N  ; +  ; R343K mutant ; Carbohydrate recognition domain ; Lipopolysaccharide inner core structure ; Gram-negative bacteria ; Glycan array ; Surface plasmon resonance ; Molecular docking ; Molecular dynamics simulations ; Synthetic glycans ; Glycan binding affinity
• 刊名：Journal of Structural Biology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：195
• 期：3
• 页码：387-395
• 全文大小：1941 K

文摘

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.