Extension and refinement of the recognition motif for Toll‐like receptor 5 activation by flagellin. Issue 4 (19th June 2018)

• Record Type: Journal Article
• Authors: Ivičak‐Kocjan, Karolina; Forstnerič, Vida; Panter, Gabriela; Jerala, Roman; Benčina, Mojca
• Other Names: Henneke Philipp guestEditor.; Broz Petr guestEditor.; Groß Olaf guestEditor.
• Is Part Of: Journal of leukocyte biology. Volume 104:Issue 4(2018)
• Page Start: 767
• Page End: 776
• Publication Date: 2018-06-19
• Subjects: flagellin -- species‐specific activation -- dimerization -- innate immunity -- Salmonella typhimurium -- TLR5; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1002/JLB.3VMA0118-035R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract: TLRs sense conserved and essential molecular components of microbes that invade multicellular organisms. The wide range of TLR agonists, differing in size and shape, is recognized either through a single or a pair of binding sites on the ectodomains of TLRs. TLR5 recognizes bacterial flagellin through two distinct binding sites on the ectodomain, the first facilitating primary binding of flagellin and the second guiding receptor dimerization necessary for signaling. The regions of flagellin recognized by TLR5 encompass key functional regions within the D1 domain of flagellin, which is also required for the assembly of functional flagella. In addition to previously identified binding sites at the N‐terminal and central segment of the TLR5 ectodomain, we extended the TLR5'‐D1 interaction interface on TLR5 and showed a species‐specific recognition relevance of this extended region. In addition, we showed that the loop and following β‐hairpin region of flagellin, previously proposed to participate in the TLR5‐flagellin dimerization interface, is not accountable for these species‐specific differences. We further identified residues that contribute to the interaction between two TLR5 ectodomains in an active signaling complex. Our work demonstrates that flagellin is recognized by TLR5 through a more extensive interaction surface than previously characterized. Abstract : Site directed mutagenesis of TLR5 and flagellin identified functional residues beyond crystallized TLR5:flagellin complex and mapped TLR5 dimerization interface.