5T7Q
TIRAP phosphoinositide-binding motif
Summary for 5T7Q
| Entry DOI | 10.2210/pdb5t7q/pdb |
| NMR Information | BMRB: 30170 |
| Descriptor | Toll/interleukin-1 receptor domain-containing adapter protein (1 entity in total) |
| Functional Keywords | tirap, phosphoinositide, phosphorylation, phosphoinositide-binding motif; structure, signaling protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 2550.20 |
| Authors | Capelluto, D.G.S.,Ellena, J.F.,Armstrong, G.,Zhao, X.,Xiao, S. (deposition date: 2016-09-05, release date: 2017-03-08, Last modification date: 2024-05-15) |
| Primary citation | Zhao, X.,Xiong, W.,Xiao, S.,Tang, T.X.,Ellena, J.F.,Armstrong, G.S.,Finkielstein, C.V.,Capelluto, D.G. Membrane targeting of TIRAP is negatively regulated by phosphorylation in its phosphoinositide-binding motif. Sci Rep, 7:43043-43043, 2017 Cited by PubMed Abstract: Pathogen-activated Toll-like receptors (TLRs), such as TLR2 and TLR4, dimerize and move laterally across the plasma membrane to phosphatidylinositol (4,5)-bisphosphate-enriched domains. At these sites, TLRs interact with the TIR domain-containing adaptor protein (TIRAP), triggering a signaling cascade that leads to innate immune responses. Membrane recruitment of TIRAP is mediated by its phosphoinositide (PI)-binding motif (PBM). We show that TIRAP PBM transitions from a disordered to a helical conformation in the presence of either zwitterionic micelles or monodispersed PIs. TIRAP PBM bound PIs through basic and nonpolar residues with high affinity, favoring a more ordered structure. TIRAP is phosphorylated at Thr28 within its PBM, which leads to its ubiquitination and degradation. We demonstrate that phosphorylation distorts the helical structure of TIRAP PBM, reducing PI interactions and cell membrane targeting. Our study provides the basis for TIRAP membrane insertion and the mechanism by which it is removed from membranes to avoid sustained innate immune responses. PubMed: 28225045DOI: 10.1038/srep43043 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
