2RIB

Crystal structure of the trimeric neck and carbohydrate recognition domain of human surfactant protein D in complex with L-glycero-D-manno-heptose

Summary for 2RIB

• Entry DOI: 10.2210/pdb2rib/pdb
• Related: 1PWB 1PWQ 2GGU 2GGX 2ORJ 2ORK 2RIA 2RIC 2RID 2RIE
• Descriptor: Pulmonary surfactant-associated protein D, CALCIUM ION, L-glycero-alpha-D-manno-heptopyranose, ... (4 entities in total)
• Functional Keywords: surfactant protein; carbohydrate recognition; domain trimeric, sugar binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 3
• Total formula weight: 52807.87

Authors

Wang, H.,Head, J.,Kosma, P.,Sheikh, S.,McDonald, B.,Smith, K.,Cafarella, T.,Seaton, B.,Crouch, E. (deposition date: 2007-10-10, release date: 2008-01-15, Last modification date: 2024-10-30)

Primary citation

Wang, H.,Head, J.,Kosma, P.,Brade, H.,Muller-Loennies, S.,Sheikh, S.,McDonald, B.,Smith, K.,Cafarella, T.,Seaton, B.,Crouch, E.
Recognition of heptoses and the inner core of bacterial lipopolysaccharides by surfactant protein d.
Biochemistry, 47:710-720, 2008

PubMed Abstract: 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-alpha-d-manno-heptose (l,d-heptose), but not by 3-deoxy-alpha-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 alpha1-->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-alpha-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.

PubMed: 18092821
DOI: 10.1021/bi7020553

Experimental method

X-RAY DIFFRACTION (1.8 Å)