Figure 4. Pleckstrin Homology (PH) domains have a β-barrel structure with an alpha helical cap.

These structures have been crystallized with either sulfate of inositol headgroups and demonstrate PI-binding at one end of the barrel with positively-charged residues and hydrophobic residues which insert into the membrane from the loop regions of the protein. PI-binding residues are depicted in blue. Dark blue residues are positively charged lysines or argininges and light blue are other inositol-headgroup coordinating residues. Residues highlighted in green insert themselves into the membrane from the loop regions, and residues highlighted in magenta are PS-binding. A. CERT PH (4HHV) coordinates a sulfate ion (orange and yellow spheres) in the inositol-binding region with Lys³², Thr³⁴, Asn³⁵, Arg⁴³, Tyr⁵⁴, Arg⁶⁶ and inserts into the membrane with Trp³³, Tyr³⁶, Ile³⁷, His³⁸, Trp⁴⁰. B. Akt PH (1UNQ) coordinates IP₄ with Glu¹⁷, Arg²³, Arg²⁵, Asn⁵², and Arg⁸⁶. It coordinates PS with Arg¹⁵ and Lys²⁰. C. Akt PH (2UZS) is known to be converted to a constitutively active form in some cancers via mutation of Glu¹⁷ to Lys¹⁷ (highlighted by the black ovals in B and C).