In silico mining and characterization of bifidobacterial lipoprotein with CHAP domain secreted in an aggregated form

• Published in: International journal of biological macromolecules Vol. 82; pp. 653 - 662
• Main Authors: Scuotto, Angelo, Romond, Pierre-Charles, Djorie, Serge, Alric, Monique, Romond, Marie-Bénédicte
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2016
• Subjects: Aggregates; Amino Acid Sequence; Animals; Bacterial Proteins - chemistry; Bacterial Proteins - isolation & purification; Bacterial Proteins - metabolism; Bacterial Proteins - pharmacology; Bifidobacteria; Bifidobacterium - immunology; Bifidobacterium - metabolism; Carbohydrates - chemistry; Computational Biology; Computer Simulation; Data Mining; Databases, Protein; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Galectin 1 - chemistry; Galectin 1 - metabolism; Galectin-1; Gene Expression Profiling; Gene Expression Regulation - drug effects; Gnotobiotic mice; Lipids - chemistry; Lipoprotein; Lipoproteins - chemistry; Lipoproteins - isolation & purification; Lipoproteins - metabolism; Lipoproteins - pharmacology; Mice; Molecular Weight; Peptides - chemistry; Protein Aggregates - immunology; Protein Binding; Protein Interaction Domains and Motifs; Protein Stability; Rheumatoid arthritis; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; TLRs; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 6 - metabolism; BC; HM mice; Bifidobacteria; Dendritic cells; Galectin-1; Lipoprotein; CHAP domain; RA mice; Aggregates; Gnotobiotic mice; Rheumatoid arthritis; TLRs; GF
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2015.10.023

Bifidobacterium breve C50 secretes a lipoprotein associated with glucose, acting in an aggregating form (>600kDa) as an agonist of TLR2/6. Similar lipoproteins were sought for in bifidobacteria. In silico, the closest homology was shown with a Bifidobacterium longum protein containing CHAP and lipobox domains. Two strains secreted aggregates whose peptides sequences aligned with the mined protein. C16:0 and C18:0 fatty acids detected in the aggregates further supported a lipoprotein structure. Glucose and mannose detected by gas chromatography were likely ligands of the lipoprotein. The binding of aggregates to galectin-1 indicated that hexosamines and galactose surrounded them. However, unlike B. breve C50, aggregate secreted by B. longum CBi0703 was unable to bind TLR2/6 likely because of a more hydrophobic structure. In gnotobiotic mice, the intake of B. longum aggregate induced, in splenic dendritic cells, the expression of genes involved in antigen presentation. A positive correlation between the number of dendritic cells and CD4+CD25+ cells was observed in mice receiving these aggregates. In conclusion, B. longum secretes a lipoprotein forming aggregates which may influence dendritic and CD4+CD25+ cell interactions independently of the TLR2/6 pathway.