4agi | pdb_00004agi
Crystal Structure of Fucose binding lectin from Aspergillus Fumigatus (AFL) in complex with seleno fucoside.
Structural highlights
FunctionLECF_ASPFU Multispecific lectin that is able to recognize L-fucose in all possible linkages (PubMed:23695231, PubMed:27058347, PubMed:24340081, PubMed:25760594). These could be found not only in decomposed plant matter in soil, which is the natural environment for A.fumigatus, but also in various epitopes on human tissues (PubMed:25760594). Mediates binding of A.fumigatus conidia to airway mucinin a fucose dependent manner (PubMed:27058347). Stimulates IL-8 production by human bronchial cells in a dose-dependent manner, contributing to the inflammatory response observed upon the exposure of a patient to A.fumigatus, and thus might be an important virulence factor involved in an early stage of A.fumigatus infection (PubMed:24340081).[1] [2] [3] [4] Publication Abstract from PubMedAspergillus fumigatus is an important allergen and opportunistic pathogen. Similarly to many other pathogens, it is able to produce lectins that may be involved in the host-pathogen interaction. We focused on the lectin AFL, which was prepared in recombinant form and characterized. Its binding properties were studied using hemagglutination and glycan array analysis. We determined the specificity of the lectin towards l-fucose and fucosylated oligosaccharides, including alpha1-6 linked core-fucose, which is an important marker for cancerogenesis. Other biologically relevant saccharides such as sialic acid, d-mannose or d-galactose were not bound. Blood group epitopes of the ABH and Lewis systems were recognized, Le(Y) being the preferred ligand among others. To provide a correlation between the observed functional characteristics and structural basis, AFL was crystallized in a complex with methyl-alpha,l-selenofucoside and its structure was solved using the SAD method. Six binding sites, each with different compositions, were identified per monomer and significant differences from the homologous AAL lectin were found. Structure-derived peptides were utilized to prepare anti-AFL polyclonal antibodies, which suggested the presence of AFL on the Aspergillus' conidia, confirming its expression in vivo. Stimulation of human bronchial cells by AFL led to IL-8 production in a dose-dependent manner. AFL thus probably contributes to the inflammatory response observed upon the exposure of a patient to A. fumigatus. The combination of affinity to human epithelial epitopes, production by conidia and pro-inflammatory activity is remarkable and shows that AFL might be an important virulence factor involved in an early stage of A. fumigatus infection. A Soluble Fucose-Specific Lectin from Aspergillus fumigatus Conidia - Structure, Specificity and Possible Role in Fungal Pathogenicity.,Houser J, Komarek J, Kostlanova N, Cioci G, Varrot A, Kerr SC, Lahmann M, Balloy V, Fahy JV, Chignard M, Imberty A, Wimmerova M PLoS One. 2013 Dec 10;8(12):e83077. doi: 10.1371/journal.pone.0083077. PMID:24340081[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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