FIGURE 15.

MARCKS(151–175) laterally sequesters the PIP₂-bound PH domain of PLC-δ₁ as well as PIP₂. (A) See text for description of cartoon. Equilibrium 1: membrane-bound MARCKS(151–175) (blue ovals represent the 13 basic residues; green ovals the five phenylalanine residues) laterally sequesters PIP₂ (red). Equilibrium 2: The PLC-δ₁ PH domain (light green) binds to PIP₂ (red) with high specificity; PIP₂ forms multiple hydrogen bonds with positively charged residues (blue + signs) in the binding pocket. Equilibrium 3: We propose that the PIP₂-bound PH domain, which contains a patch of acidic residues (red − signs) on its surface, is (like PIP₂) sequestered electrostatically by the membrane-bound MARCKS(151–175). Panel B shows the potential produced by PIP₂ (yellow) on a PC membrane. Panel C shows the potential produced by PIP₂-bound PH domain (green) on a PC membrane as viewed from the side. Panel D illustrates the view from the top of the membrane: −25 mV and +25 mV potential profiles are shown in red and blue; salt concentration = 100 mM.