title: Modulation of microtubule dynamics by a TIR domain protein from the intracellular pathogen Brucella melitensis.
abstract: TIR (Toll/interleukin-1 receptor) domain-containing proteins play a crucial role in innate immunity in eukaryotes. Brucella is a highly infectious intracellular bacterium that encodes a TIR domain protein (TcpB) to subvert host innate immune responses to establish a beneficial niche for pathogenesis. TcpB inhibits NF-κB (nuclear factor κB) activation and pro-inflammatory cytokine secretions mediated by TLR (Toll-like receptor) 2 and TLR4. In the present study, we have demonstrated that TcpB modulates microtubule dynamics by acting as a stabilization factor. TcpB increased the rate of nucleation as well as the polymerization phases of microtubule formation in a similar manner to paclitaxel. TcpB could efficiently inhibit nocodazole- or cold-induced microtubule disassembly. Microtubule stabilization by TcpB is attributed to the BB-loop region of the TIR domain, and a point mutation affected the microtubule stabilization as well as the TLR-suppression properties of TcpB.
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Girish K
authors.initials: GK
authors.lastname: Radhakrishnan
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Harms
authors.forename: Gary A
authors.initials: GA
authors.lastname: Splitter
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D017347:Brucella melitensis / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D017472:Receptors, Interleukin-1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D015739:Nocodazole