6SWS

The DBB dimerization domain of B-cell adaptor for PI3K (BCAP) is required for down regulation of inflammatory signalling through the Toll-like receptor pathway

6SWS の概要

• エントリーDOI: 10.2210/pdb6sws/pdb
• 分子名称: Phosphoinositide 3-kinase adapter protein 1 (1 entity in total)
• 機能のキーワード: dbb, tig/ipt, transcription factor, transcription
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 62370.35

構造登録者

Lauenstein, J.U.,Scherm, M.J.,Udgata, A.,Moncrieffe, M.C.,Fisher, D.,Gay, N.J. (登録日: 2019-09-23, 公開日: 2020-02-19, 最終更新日: 2024-05-15)

主引用文献

Lauenstein, J.U.,Scherm, M.J.,Udgata, A.,Moncrieffe, M.C.,Fisher, D.I.,Gay, N.J.
Negative Regulation of TLR Signaling by BCAP Requires Dimerization of Its DBB Domain.
J Immunol., 204:2269-2276, 2020

PubMed Abstract: The B cell adaptor protein (BCAP) is a multimodular regulator of inflammatory signaling in diverse immune system cells. BCAP couples TLR signaling to phosphoinositide metabolism and inhibits MyD88-directed signal transduction. BCAP is recruited to the TLR signalosome forming multitypic interactions with the MAL and MyD88 signaling adaptors. In this study, we show that indirect dimerization of BCAP TIR is required for negative regulation of TLR signaling. This regulation is mediated by a transcription factor Ig (TIG/IPT) domain, a fold found in the NF-κB family of transcription factors. We have solved the crystal structure of the BCAP TIG and find that it is most similar to that of early B cell factor 1 (EBF1). In both cases, the dimer is stabilized by a helix-loop-helix motif at the C terminus and interactions between the β-sheets of the Ig domains. BCAP is exclusively localized in the cytosol and is unable to bind DNA. Thus, the TIG domain is a promiscuous dimerization module that has been appropriated for a range of regulatory functions in gene expression and signal transduction.

PubMed: 32198144
DOI: 10.4049/jimmunol.1901210

実験手法

X-RAY DIFFRACTION (3 Å)