Molecular Dynamics Studies of Side Chain Effect on the β-1,3-<scp>d</scp>-Glucan Triple Helix in Aqueous Solution

Okobira, Tadashi; Miyoshi, Keita; Uezu, Kazuya; Sakurai, Kazuo; Shinkai, Seiji

doi:10.1021/bm700511d

Cited by 75 publications

(52 citation statements)

References 41 publications

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“…3). The stoichiometry for the interaction between GNBP3-Nter and laminarin was close to a ratio of 1-3 (n ϭ 2.51), consistent with a triple helix organization of the laminarin in solution (39). The binding affinity is K A ϭ 2.12 ϫ 10 6 Ϯ 0.4 ϫ 10…”

Section: Resultssupporting

confidence: 53%

The N-terminal Domain of Drosophila Gram-negative Binding Protein 3 (GNBP3) Defines a Novel Family of Fungal Pattern Recognition Receptors

Mishima

Quintin

Aimanianda

et al. 2009

Journal of Biological Chemistry

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Gram-negative binding protein 3 (GNBP3), a pattern recognition receptor that circulates in the hemolymph of Drosophila, is responsible for sensing fungal infection and triggering Toll pathway activation. Here, we report that GNBP3 N-terminal domain binds to fungi upon identifying long chains of ␤-1,3-glucans in the fungal cell wall as a major ligand. Interestingly, this domain fails to interact strongly with short oligosaccharides. The crystal structure of GNBP3-Nter reveals an immunoglobulin-like fold in which the glucan binding site is masked by a loop that is highly conserved among glucan-binding proteins identified in several insect orders. Structure-based mutagenesis experiments reveal an essential role for this occluding loop in discriminating between short and long polysaccharides. The displacement of the occluding loop is necessary for binding and could explain the specificity of the interaction with long chain structured polysaccharides. This represents a novel mechanism for ␤-glucan recognition.

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Section: Resultssupporting

confidence: 53%

The N-terminal Domain of Drosophila Gram-negative Binding Protein 3 (GNBP3) Defines a Novel Family of Fungal Pattern Recognition Receptors

Mishima

Quintin

Aimanianda

et al. 2009

Journal of Biological Chemistry

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“…To investigate the ␤-1,3-glucanrecognition mechanism by ␤GRP N102, the surface plasmon resonance (SPR) data were first analyzed. In aqueous solution, ␤-1,3-glucan forms a stable triple-helical structure and is known to be converted into a random coil or a single helix by chemical or physical treatments (18)(19)(20). Previous studies have shown that NaOH treatment alters the structure of laminaran (soluble ␤-1,3-glucan) from a triple-helical structure into a partially opened triple-helical structure, and it was indicated that even after neutralization, the partially opened structure was maintained for up to 20 days (21,22).…”

Section: Resultsmentioning

confidence: 99%

Solution structure of the silkworm βGRP/GNBP3 N-terminal domain reveals the mechanism for β-1,3-glucan-specific recognition

Takahasi

Ochiai

Horiuchi

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The ␤-1,3-glucan recognition protein (␤GRP)/Gram-negative bacteriabinding protein 3 (GNBP3) is a crucial pattern-recognition receptor that specifically binds ␤-1,3-glucan, a component of fungal cell walls. It evokes innate immunity against fungi through activation of the prophenoloxidase (proPO) cascade and Toll pathway in invertebrates. The ␤GRP consists of an N-terminal ␤-1,3-glucan-recognition domain and a C-terminal glucanase-like domain, with the former reported to be responsible for the proPO cascade activation. This report shows the solution structure of the N-terminal ␤-1,3-glucan recognition domain of silkworm ␤GRP. Although the N-terminal domain of ␤GRP has a ␤-sandwich fold, often seen in carbohydrate-binding modules, both NMR titration experiments and mutational analysis showed that ␤GRP has a binding mechanism which is distinct from those observed in previously reported carbohydarate-binding domains. Our results suggest that ␤GRP is a ␤-1,3-glucan-recognition protein that specifically recognizes a triple-helical structure of ␤-1,3-glucan.phenol oxidase ͉ innate immunity ͉ pattern recognition

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“…Thus, the presence of the O-and N-linked mannosyl proteins at the Candida cell surface is required for proper priming, supposedly by aiding cell priming by an additional cell wall component. Of note, although, under aqueous conditions, long chains of purified b-glucan form a right-handed triple helical complex that is required for the proper binding to pattern recognition receptors (27)(28)(29), purified mannan might not have the required structure to be recognized by its receptor, offering an alternative explanation for the lack of priming induced by pure mannans. Different biological effects of mannans were reported, including induction of proinflammatory cytokines (19,30) and of IL-10 (31).…”

Section: Discussionmentioning

confidence: 99%

Candida albicans Primes TLR Cytokine Responses through a Dectin-1/Raf-1–Mediated Pathway

Ifrim¹,

Joosten²,

Kullberg³

et al. 2013

The Journal of Immunology

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The immune system is essential to maintain homeostasis with resident microbial populations, ensuring that the symbiotic host–microbial relationship is maintained. In parallel, commensal microbes significantly shape mammalian immunity at the host mucosal surface, as well as systemically. Candida albicans is an opportunistic pathogen that lives as a commensal on skin and mucosa of healthy individuals. Little is known about its capacity to modulate responses toward other microorganisms, such as colonizing bacteria (e.g., intestinal microorganisms). The aim of this study was to assess the cytokine production of PBMCs induced by commensal bacteria when these cells were primed by C. albicans. We show that C. albicans and β-1,3-glucan induce priming of human primary mononuclear cells and this leads to enhanced cytokine production upon in vitro stimulation with TLR ligands and bacterial commensals. This priming requires the β-1,3-glucan receptor dectin-1 and the noncanonical Raf-1 pathway. In addition, although purified mannans cannot solely mediate the priming, the presence of mannosyl residues in the cell wall of C. albicans is nevertheless required. In conclusion, C. albicans is able to modify cytokine responses to TLR ligands and colonizing bacteria, which is likely to impact the inflammatory reaction during mucosal diseases.

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Molecular Dynamics Studies of Side Chain Effect on the β-1,3-d-Glucan Triple Helix in Aqueous Solution

Cited by 75 publications

References 41 publications

The N-terminal Domain of Drosophila Gram-negative Binding Protein 3 (GNBP3) Defines a Novel Family of Fungal Pattern Recognition Receptors

The N-terminal Domain of Drosophila Gram-negative Binding Protein 3 (GNBP3) Defines a Novel Family of Fungal Pattern Recognition Receptors

Solution structure of the silkworm βGRP/GNBP3 N-terminal domain reveals the mechanism for β-1,3-glucan-specific recognition

Candida albicans Primes TLR Cytokine Responses through a Dectin-1/Raf-1–Mediated Pathway

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