4C7M

The crystal structure of TcpB or BtpA TIR domain

4C7M の概要

• エントリーDOI: 10.2210/pdb4c7m/pdb
• 分子名称: Toll/interleukin-1 receptor domain-containing protein (2 entities in total)
• 機能のキーワード: signaling protein, protein
• 由来する生物種: Brucella melitensis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 60240.48

構造登録者

Alaidarous, M.,Ve, T.,Casey, L.W.,Valkov, E.,Ullah, M.O.,Schembri, M.A.,Mansell, A.,Sweet, M.J.,Kobe, B. (登録日: 2013-09-23, 公開日: 2013-12-04, 最終更新日: 2023-12-20)

主引用文献

Alaidarous, M.,Ve, T.,Casey, L.W.,Valkov, E.,Ericsson, D.J.,Ullah, M.O.,Schembri, M.A.,Mansell, A.,Sweet, M.J.,Kobe, B.
Mechanism of bacterial interference with TLR4 signaling by Brucella Toll/interleukin-1 receptor domain-containing protein TcpB.
J.Biol.Chem., 289:654-668, 2014

PubMed Abstract: Upon activation of Toll-like receptors (TLRs), cytoplasmic Toll/interleukin-1 receptor (TIR) domains of the receptors undergo homo- or heterodimerization. This in turn leads to the recruitment of adaptor proteins, activation of transcription factors, and the secretion of pro-inflammatory cytokines. Recent studies have described the TIR domain-containing protein from Brucella melitensis, TcpB (BtpA/Btp1), to be involved in virulence and suppression of host innate immune responses. TcpB interferes with TLR4 and TLR2 signaling pathways by a mechanism that remains controversial. In this study, we show using co-immunoprecipitation analyses that TcpB interacts with MAL, MyD88, and TLR4 but interferes only with the MAL-TLR4 interaction. We present the crystal structure of the TcpB TIR domain, which reveals significant structural differences in the loop regions compared with other TIR domain structures. We demonstrate that TcpB forms a dimer in solution, and the crystal structure reveals the dimerization interface, which we validate by mutagenesis and biophysical studies. Our study advances the understanding of the molecular mechanisms of host immunosuppression by bacterial pathogens.

PubMed: 24265315
DOI: 10.1074/jbc.M113.523274

実験手法

X-RAY DIFFRACTION (2.57 Å)