Mahesh Chandra Patra Author

Short Communication Open Access

Mechanism of phosphatidylinositol-dependent membrane localization of Toll/interleukin 1 receptor domaincontaining adaptor protei

Author(s):

Mahesh Chandra Patra

The Toll/interleukin 1 receptor (TIR) domain-containing adaptor protein (TIRAP) regulates Toll-like receptor (TLR) 2, TLR4, TLR7, and TLR9 signaling pathways. TIRAP anchors to phosphatidylinositol (PI) 4,5-bisphosphate (PIP2) on the plasma membrane and PI (3,4,5)-trisphosphate (PIP3) on the endosomal membrane and assists in recruitment of the myeloid differentiation primary response 88 protein to activated TLRs. To date, the structure and mechanism of TIRAP’s membrane association are only partially understood. Here, we modeled an all-residue TIRAP dimer using homology modeling, threading, and protein-protein docking strategies. Molecular dynamics simulations revealed that PIP2 creates a stable microdomain in a dipalmitoylphosphatidylcholine bilayer, providing TIRAP with its physio... view more»

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