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Extension and refinement of the recognition motif for Toll‐like receptor 5 activation by flagellin
Author(s) -
IvičakKocjan Karolina,
Forstnerič Vida,
Panter Gabriela,
Jerala Roman,
Benčina Mojca
Publication year - 2018
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.3vma0118-035r
Subject(s) - flagellin , biology , motif (music) , toll like receptor , toll , receptor , computational biology , pattern recognition receptor , microbiology and biotechnology , genetics , innate immune system , physics , acoustics
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.