title: NMR study of short β(1-3)-glucans provides insights into the structure and interaction with Dectin-1.
abstract: β(1-3)-Glucans, abundant in fungi, have the potential to activate the innate immune response against various pathogens. Although part of the action is exerted through the C-type lectin-like receptor Dectin-1, details of the interaction mechanism with respect to glucan chain-length remain unclear. In this study, we investigated a set of short β(1-3)-glucans with varying degree of polymerization (DP); 3, 6, 7, 16, and laminarin (average DP; 25), analyzing the relationship between the structure and interaction with the C-type lectin-like domain (CTLD) of Dectin-1. The interaction of short β(1-3)-glucans (DP6, DP16, and laminarin) with the CTLD of Dectin-1 was systematically analyzed by (1)H-NMR titration as well as by saturation transfer difference (STD)-NMR. The domain interacted weakly with DP6, moderately with DP16 and strongly with laminarin, the latter plausibly forming oligomeric protein-laminarin complexes. To obtain structural insights of short β(1-3)-glucans, the exchange rates of hydroxy protons were analyzed by deuterium induced (13)C-NMR isotope shifts. The hydroxy proton at C4 of laminarin has slower exchange with the solvent than those of DP7 and DP16, suggesting that laminarin has a secondary structure. Diffusion ordered spectroscopy revealed that none of the short β(1-3)-glucans including laminarin forms a double or triple helix in water. Insights into the interaction of the short β(1-3)-glucans with Dectin-1 CTLD provide a basis to understand the molecular mechanisms of β-glucan recognition and cellular activation by Dectin-1.
authors.affiliation: Structural Glycobiology Team, Systems Glycobiology Research Group, RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hanashima
authors.forename: Akemi
authors.initials: A
authors.lastname: Ikeda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Adachi
authors.forename: Naohito
authors.initials: N
authors.lastname: Ohno
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaguchi
mesh_terms: D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003903:Deuterium; D005936:Glucans / Q000737:chemistry; D037181:Lectins, C-Type / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D013057:Spectrum Analysis / Q000379:methods; D013329:Structure-Activity Relationship; D047071:beta-Glucans / Q000737:chemistry* / Q000378:metabolism*; D000099181:Dectin-1
chemical_list: D003903:Deuterium; D005936:Glucans; D037181:Lectins, C-Type; D047071:beta-Glucans; D000099181:Dectin-1; C008247:laminaran