Section 46
Chapter 45,844

Duplicated binding sites for (1-->3) -beta-D-glucan in the horseshoe crab coagulation factor G: implications for a molecular basis of the pattern recognition in innate immunity

Takaki, Y.; Seki, N.; Kawabata Si, S.-i.; Iwanaga, S.; Muta, T.

Journal of Biological Chemistry 277(16): 14281-14287


ISSN/ISBN: 0021-9258
PMID: 11830593
DOI: 10.1074/jbc.m200177200
Accession: 045843326

The horseshoe crab factor G, a heterodimeric serine protease zymogen, is activated by (1-->3)-beta-D-glucan on fungal cell walls. The activation initiates the hemolymph-clotting cascade, a critical reaction for the defense against microorganisms. In the present study, we identified the domain responsible for the glucan recognition by factor G and characterized its interaction with (1-->3)-beta-d-glucan and its derivatives. Among three domains in subunit alpha of factor G, identified as the glucan-binding domain, was the COOH-terminal xylanase Z-like domain composed of two tandem-repeating units, each of which exhibits sequence similarities to the cellulose-binding domains of bacterial xylanases. Each of the single units bound to the glucan with lower affinities, and the association constant increased two orders with the tandem-repeating structure (K(a) = 8.0 x 10(8) m(-1)). In addition to longer glucans, (1-->3)-beta-D-glucan oligosaccharides incapable of activating factor G bound also to factor G and competitively inhibited the zymogen activation. The minimum structure required for the binding was a (1-->3)-beta-d-glucan disaccharide, indicating that conformation-dependent structures are not essential for the recognition. Therefore, increasing avidity by multivalent binding sites with low affinities to simple structures on biologically active polymers may be one of the principles that allows stable and specific recognition of pathogens by pattern recognition receptors in innate immunity.

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