title: Molecular insights into the binding of phosphoinositides to the TH domain region of TIPE proteins.
abstract: Phosphatidylinositols and their phosphorylated derivatives, phosphoinositides, play a central role in regulating diverse cellular functions. These phospholipids have been shown to interact with the hydrophobic TH domain of the tumor necrosis factor (TNF)-α-induced protein 8 (TIPE) family of proteins. However, the precise mechanism of interaction of these lipids is unclear. Here we report the binding mode and interactions of these phospholipids in the TH domain, as elucidated using molecular docking and simulations. Results indicate that phosphoinositides bind to the TH domain in a similar way by inserting their lipid tails in the hydrophobic cavity. The exposed head group is stabilized by interactions with critical positively charged residues on the surface of these proteins. Further MD simulations confirmed the dynamic stability of these lipids in the TH domain. This computational analysis thus provides insight into the binding mode of phospholipids in the TH domain of the TIPE family of proteins. Graphical abstract A phosphoinositide (phosphatidylinositol 4-phosphate; PtdIns4P) docked to TIPE2.
authors: Department of Biology, College of Science, United Arab Emirates University, PO Box 15551, Al Ain, United Arab Emirates.
authors: Priya
authors: P
authors: Antony
authors: Department of Biology, College of Science, United Arab Emirates University, PO Box 15551, Al Ain, United Arab Emirates.
authors: Bincy
authors: B
authors: Baby
authors: Department of Biology, College of Science, United Arab Emirates University, PO Box 15551, Al Ain, United Arab Emirates. ranjit.v@uaeu.ac.ae.
authors: Ranjit
authors: R
authors: Vijayan
mesh_terms: D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010716:Phosphatidylinositols / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010716:Phosphatidylinositols; C552057:TNFAIP8L2 protein, human; C000593651:TNFAIP8L3 protein, human
keywords: Phosphatidylinositols; Phosphoinositides; TH domain; TIPE2; TIPE3