Structural insights into the PIP2 recognition by syntenin-1 PDZ domain.
Lipid-mediated regulatory mechanism of the C-terminal ligand binding to PDZ domains is not fully understood, despite their roles in subcellular organization. Here, we provide structural insights into the phosphatidylinositol 4,5-bisphosphate (PIP(2)) recognition mode of a PDZ domain, as revealed from the crystal structure of the phosphate-bound PDZ domain. Two adjacent phosphate ions bind to the basic residues close to the amino terminus of the alpha2 helix in the Tamalin PDZ domain, reflecting an interaction mode of the two phosphate groups of PIP(2). Based on the observed location of the two phosphate molecules within the PDZ domain, we built the docking model of PIP(2) with the PDZ domain of the well-known PIP(2)-binding protein, syntenin-1. This model suggests that the hydrophobic diacylglycerol group of PIP(2) could contact the ligand-binding groove of the PDZ domain. These structural features well explain biological phenomena, which were previously reported for the PIP(2)-mediated PDZ ligand-binding regulation.
Sugi
Takuma
T
Department of Molecular Biology, Biomolecular Engineering Research Institute (BERI), 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan.
Oyama
Takuji
T
Morikawa
Kosuke
K
Jingami
Hisato
H
D001665:Binding Sites; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D053676:Syntenins / Q000737:chemistry* / Q000648:ultrastructure*
D019269:Phosphatidylinositol 4,5-Diphosphate; D053676:Syntenins