Structural Insights into Recognition of Triple-helical β-Glucans by an Insect Fungal Receptor

The innate ability to detect pathogens is achieved by pattern recognition receptors, which recognize non-self-components such as beta 1,3-glucan. beta 1,3-Glucans form a triple-helical structure stabilized by interchain hydrogen bonds. beta 1,3-Glucan recognition protein (beta GRP)/Gram-negative bacteria-binding protein 3 (GNBP3), one of the pattern recognition receptors, binds to long, structured beta 1,3-glucan to initiate innate immune response. However, binding details and how specificity is achieved in such receptors remain important unresolved issues. We solved the crystal structures of the N-terminal beta 1,3-glucan recognition domain of beta GRP/GNBP3 (beta GRP-N) in complex with the beta 1,3-linked glucose hexamer, laminarihexaose. In the crystals, three structured laminarihexaoses simultaneously interact through six glucose residues (two from each chain) with one beta GRP-N. The spatial arrangement of the laminarihexaoses bound to beta GRP-N is almost identical to that of a beta 1,3-glucan triple-helical structure. Therefore, our crystallographic structures together with site-directed mutagenesis data provide a structural basis for the unique recognition by such receptors of the triple-helical structure of beta 1,3-glucan.