TRIMERIC STRUCTURE OF A C-TYPE MANNOSE-BINDING PROTEIN

Background: Mannose-binding proteins (MBPs) are C-type (Ca2+-dependent ) animal lectins found in serum. They recognize cell-surface oligosacc haride structures characteristic of pathogenic bacteria and fungi, and trigger the neutralization of these organisms. Like most lectins, MBP s display weak intrinsic affinity for monovalent sugar ligands, but bi nd avidly to multivalent ligands. Results: We report physical studies in solution and the crystal structure determined at 1.8 Angstrom Bragg spacings of a trimeric fragment of MBP-A, containing the carbohydrate -recognition domain (CRD) and the neck domain that links the carboxy-t erminal CRD to the collagen-like portion of the intact molecule. The n eck consists of a parallel triple-stranded coiled coil of alpha-helice s linked by four residues to the CRD. The isolated neck peptide does n ot form stable. helices in aqueous solution. The previously characteri zed carbohydrate-binding sites lie at the distal end of the trimer and are separated from each other by 53 Angstrom. Conclusions: The carboh ydrate-binding sites in MBP-A are too far apart for a single trimer to bind multivalently to a typical mammalian high-mannose oligosaccharid e. Thus MBPs can recognize pathogens selectively by binding avidly onl y to the widely spaced, repetitive sugar arrays on pathogenic cell sur faces. Sequence alignments reveal that other C-type lectins are likely to have a similar oligomeric structure, but differences in their deta iled organization will have an important role in determining their int eractions with oligosaccharides.