5FOR

Cryptic TIR

Summary for 5FOR

• Entry DOI: 10.2210/pdb5for/pdb
• Descriptor: PHOSPHOINOSITIDE 3-KINASE ADAPTER PROTEIN 1, PENTAETHYLENE GLYCOL, 5-amino-2,4,6-triiodobenzene-1,3-dicarboxylic acid, ... (4 entities in total)
• Functional Keywords: cell cycle, tir, immume response
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm : Q6ZUJ8
• Total number of polymer chains: 1
• Total formula weight: 16820.44

Authors

Halabi, S.,Gay, N.J.,Moncrieffe, M.C. (deposition date: 2015-11-25, release date: 2016-12-07, Last modification date: 2025-04-09)

Primary citation

Halabi, S.,Sekine, E.,Verstak, B.,Gay, N.J.,Moncrieffe, M.C.
Structure of the Toll/Interleukin-1 Receptor (TIR) Domain of the B-cell Adaptor That Links Phosphoinositide Metabolism with the Negative Regulation of the Toll-like Receptor (TLR) Signalosome.
J. Biol. Chem., 292:652-660, 2017

PubMed Abstract: Ligand binding to Toll-like receptors (TLRs) results in dimerization of their cytosolic Toll/interleukin-1 receptor (TIR) domains and recruitment of post-receptor signal transducers into a complex signalosome. TLR activation leads to the production of transcription factors and pro-inflammatory molecules and the activation of phosphoinositide 3-kinases (PI3K) in a process that requires the multimodular B-cell adaptor for phosphoinositide 3-kinase (BCAP). BCAP has a sequence previously proposed as a "cryptic" TIR domain. Here, we present the structure of the N-terminal region of human BCAP and show that it possesses a canonical TIR fold. Dimeric BCAP associates with the TIR domains of TLR2/4 and MAL/TIRAP, suggesting that it is recruited to the TLR signalosome by multitypic TIR-TIR interactions. BCAP also interacts with the p85 subunit of PI3K and phospholipase Cγ, enzymes that deplete plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2), and these interactions provide a molecular explanation for BCAP-mediated down-regulation of inflammatory signaling.

PubMed: 27909057
DOI: 10.1074/jbc.M116.761528

Experimental method

X-RAY DIFFRACTION (2.5 Å)