Recognition of Heptoses and the Inner Core of Bacterial Lipopolysaccharides by Surfactant Protein D
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- 作者：Hua Wang ; James Head ; Paul Kosma ; Helmut Brade ; Sven Mü ; ller-Loennies ; Sharmin Sheikh ; Barbara McDonald ; Kelly Smith ; Tanya Cafarella ; Barbara Seaton ; Erika Crouch
- 刊名：Biochemistry
- 出版年：2008
- 出版时间：January 15, 2008
- 年：2008
- 卷：47
- 期：2
- 页码：710 - 720
- 全文大小：607K
- 年卷期：v.47,no.2(January 15, 2008)
- ISSN：1520-4995
文摘
Lipopolysaccharides (LPS) of Gram-negative bacteria are important mediators of bacterialvirulence that can elicit potent endotoxic effects. Surfactant protein D (SP-D) shows specific interactionswith LPS, both in vitro and in vivo. These interactions involve binding of the carbohydrate recognitiondomain (CRD) to LPS oligosaccharides (OS); however, little is known about the mechanisms of LPSrecognition. Recombinant neck+CRDs (NCRDs) provide an opportunity to directly correlate bindinginteractions with a crystallographic analysis of the binding mechanism. In these studies, we examined theinteractions of wild-type and mutant trimeric NCRDs with rough LPS (R-LPS). Although rat NCRDsbound more efficiently than human NCRDs to Escherichia coli J-5 LPS, both proteins exhibited efficientbinding to solid-phase Rd2-LPS and to Rd2-LPS aggregates presented in the solution phase. Involvementof residues flanking calcium at the sugar binding site was demonstrated by reciprocal exchange of lysineand arginine at position 343 of rat and human CRDs. The lectin activity of hNCRDs was inhibited byspecific heptoses, including L-glycero-
-D-manno-heptose (L,D-heptose), but not by 3-deoxy--D-manno-oct-2-ulosonic acid (Kdo). Crystallographic analysis of the hNCRD demonstrated a novel binding orientationfor L,D-heptose, involving the hydroxyl groups of the side chain. Similar binding was observed for asynthetic 1
3-linked heptose disaccharide corresponding to heptoses I and II of the inner core regionin many LPS. 7-O-Carbamoyl-L,D-heptose and D-glycero--D-manno-heptose were bound via ring hydroxylgroups. Interactions with the side chain of inner core heptoses provide a potential mechanism for therecognition of diverse types of LPS by SP-D.
-D-manno-heptose (L,D-heptose), but not by 3-deoxy--D-manno-oct-2-ulosonic acid (Kdo). Crystallographic analysis of the hNCRD demonstrated a novel binding orientationfor L,D-heptose, involving the hydroxyl groups of the side chain. Similar binding was observed for asynthetic 13-linked heptose disaccharide corresponding to heptoses I and II of the inner core regionin many LPS. 7-O-Carbamoyl-L,D-heptose and D-glycero--D-manno-heptose were bound via ring hydroxylgroups. Interactions with the side chain of inner core heptoses provide a potential mechanism for therecognition of diverse types of LPS by SP-D.