title: The N-terminal domain of Drosophila Gram-negative binding protein 3 (GNBP3) defines a novel family of fungal pattern recognition receptors.
abstract: 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 beta-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 beta-glucan recognition.
authors.affiliation: Centre de Biophysique Moléculaire, UPR 4301 CNRS, 45071 Orléans Cedex 2, France.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Mishima
authors.forename: Jessica
authors.initials: J
authors.lastname: Quintin
authors.forename: Vishukumar
authors.initials: V
authors.lastname: Aimanianda
authors.forename: Christine
authors.initials: C
authors.lastname: Kellenberger
authors.forename: Franck
authors.initials: F
authors.lastname: Coste
authors.forename: Cecile
authors.initials: C
authors.lastname: Clavaud
authors.forename: Charles
authors.initials: C
authors.lastname: Hetru
authors.forename: Jules A
authors.initials: JA
authors.lastname: Hoffmann
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Latgé
authors.forename: Dominique
authors.initials: D
authors.lastname: Ferrandon
authors.forename: Alain
authors.initials: A
authors.lastname: Roussel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D012831:Bombyx; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray / Q000379:methods; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism*; D004331:Drosophila melanogaster; D005656:Fungal Proteins / Q000737:chemistry*; D006458:Hemolymph / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011134:Polysaccharides / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D047071:beta-Glucans / Q000737:chemistry
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D005656:Fungal Proteins; C516487:GNBP3 protein, Drosophila; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D011134:Polysaccharides; D047071:beta-Glucans
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