title: Distinctive Recognition of Flagellin by Human and Mouse Toll-Like Receptor 5.
abstract: Toll-like receptor 5 (TLR5) is a receptor of the innate immune system that recognizes flagellin from certain bacterial species and triggers an inflammatory response. The Salmonella dublin flagellin in complex with zebrafish TLR5 has been crystallized previously. In the present study, we extrapolate the structure of this complex using structure-guided mutagenesis to determine the recognition modes of human and mouse TLR5 receptors and demonstrate species-specific differences in flagellin recognition. In general, the recognition mode of the mouse receptor can be said to be more robust in comparison to that of the human receptor. All-atom molecular dynamics simulation showed differences between the two receptors within the primary binding region. Using a functional motility assay, we show that although the highly conserved area of the flagellin analyzed in this study encompasses key structural requirements for flagella formation, a direct correlation between immune recognition and structure on the level of amino acid residues is not observed.
authors.affiliation: Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
authors.forename: Vida
authors.initials: V
authors.lastname: Forstnerič
authors.affiliation: Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
authors.forename: Karolina
authors.initials: K
authors.lastname: Ivičak-Kocjan
authors.affiliation: Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
authors.forename: Ajasja
authors.initials: A
authors.lastname: Ljubetič
authors.affiliation: Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.|Centre of Excellence EN-FIST, Ljubljana, Slovenia.
authors.forename: Roman
authors.initials: R
authors.lastname: Jerala
authors.affiliation: Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.|Centre of Excellence EN-FIST, Ljubljana, Slovenia.
authors.forename: Mojca
authors.initials: M
authors.lastname: Benčina
mesh_terms: D000818:Animals; D005408:Flagellin / Q000235:genetics / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D012475:Salmonella / Q000235:genetics / Q000276:immunology*; D013045:Species Specificity; D051198:Toll-Like Receptor 5 / Q000235:genetics
chemical_list: C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D005408:Flagellin