Structure of the GRP1 PH domain.

<p><b>A</b> The crystal structure of GRP1-PH (PDB 1FGY). The I(1,3,4,5)P₄ headgroup and the sidechains of two key residues (K279 and R284) are shown as van der Waals spheres. The protein is oriented such that the bilayer normal, as determined by previous MD simulations, is vertical (<i>i.e.</i> defines the <i>z</i> axis). <b>B</b> Electrostatic potential of GRP1-PH projected onto the solvent-accessible surface, showing the large positive electrostatic potential around the I(1,3,4,5)P₄ binding site. The electrostatic potential was calculated in the absence of I(1,3,4,5)P₄ using APBS as described in the main text and is coloured from −5 kT/<i>e</i> (red) to +5 kT/<i>e</i> (blue). The protein is shown in the same orientation as in <b>A</b> and the molecular dipole moment (calculated using the Protein Dipole Moments Server (<a href="http://bioinfo.weizmann.ac.il/dipol/" target="_blank">http://bioinfo.weizmann.ac.il/dipol/</a>; <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002617#pcbi.1002617-Felder1" target="_blank">[70]</a>) is indicated by a black arrow. <b>C</b> Snapshot from a BD simulation showing the protein solvent-accessible surface coloured by electrostatic potential, with the molecular dipole moment shown as a black arrow as in <b>B</b>. The POPC lipid bilayer is shown as a white surface with the single PI(3,4,5)P₃ molecule shown in black.