(A) High-affinity orientation of FGF2, showing all the known PI(4,5)P2-binding site residues (K127, R128, K133) as well as the previously undetermined binding site residues (K34, K137, K143). (B) Low-affinity orientation of FGF2 in which the binding site residues lose contact with PI(4,5)P2 and point away from the PI(4,5)P2 head groups. FGF2 is rendered as green cartoon, and its C95 and C77 residues are shown as van der Waals (vdW) spheres and highlighted by text in the figure. The key binding pocket residues (K127, R128, K133) are shown as blue vdW spheres, and the additional binding site residues (K34, K137, K143) are shown as purple vdW spheres. Lipids are colored as gray vdW spheres (POPC phosphate atoms), red vdW spheres [PI(4,5)P2 bisphosphates], cyan vdW spheres [inositol ring in PI(4,5)P2], orange vdW spheres [phosphate linking the fatty acid chains and the inositol ring in PI(4,5)P2], and white vdW spheres [fatty acid chains in PI(4,5)P2]. Water molecules and ions are not shown for clarity.