Modulation of microtubule dynamics by a TIR domain protein from the intracellular pathogen Brucella melitensis

作者：Radhakrishnan Girish K; Harms Jerome S; Splitter Gary A^*

来源：Biochemical Journal, 2011, 439: 79-83.

DOI：10.1042/BJ20110577

• BB-loop
• Brucella
• microtubule
• Toll-like receptor (TLR)
• Toll/interleukin-1 receptor domain (TIR domain)
• Toll/interleukin-1 receptor domain-containing adaptor protein (TIRAP)

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-kappa B (nuclear factor kappa B) 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.

• 出版日期2011-10-1