Recognition of heptoses and the inner core of bacterial lipopolysaccharides by surfactant protein D

Hua Wang, James Head, Paul Kosma, Helmut Brade, Sven Müller-Loennies, Sharmin Sheikh, Barbara McDonald, Kelly Smith, Tanya Cafarella, Barbara Seaton, Erika Crouch

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Lipopolysaccharides (LPS) of Gram-negative bacteria are important mediators of bacterial virulence that can elicit potent endotoxic effects. Surfactant protein D (SP-D) shows specific interactions with LPS, both in vitro and in vivo. These interactions involve binding of the carbohydrate recognition domain (CRD) to LPS oligosaccharides (OS); however, little is known about the mechanisms of LPS recognition. Recombinant neck+CRDs (NCRDs) provide an opportunity to directly correlate binding interactions with a crystallographic analysis of the binding mechanism. In these studies, we examined the interactions of wild-type and mutant trimeric NCRDs with rough LPS (R-LPS). Although rat NCRDs bound more efficiently than human NCRDs to Escherichia coli J-5 LPS, both proteins exhibited efficient binding to solid-phase Rd2-LPS and to Rd2-LPS aggregates presented in the solution phase. Involvement of residues flanking calcium at the sugar binding site was demonstrated by reciprocal exchange of lysine and arginine at position 343 of rat and human CRDs. The lectin activity of hNCRDs was inhibited by specific heptoses, including L-glycero-α-D-manno-heptose (L,D-heptose), but not by 3-deoxy-α-D- manno-oct-2-ulosonic acid (Kdo). Crystallographic analysis of the hNCRD demonstrated a novel binding orientation for L,D-heptose, involving the hydroxyl groups of the side chain. Similar binding was observed for a synthetic α1→3-linked heptose disaccharide corresponding to heptoses I and II of the inner core region in many LPS. 7-O-Carbamoyl-L,D-heptose and D-glycero-α-D-manno-heptose were bound via ring hydroxyl groups. Interactions with the side chain of inner core heptoses provide a potential mechanism for the recognition of diverse types of LPS by SP-D.

Original languageEnglish
Pages (from-to)710-720
Number of pages11
Issue number2
StatePublished - Jan 15 2008


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