Fig. 4.

PE and the Charge Balance Rule. A cytoplasmic EMD is shown containing a mixture of negatively and positively charged amino acids. Left Panel. According to the Charge Balance Rule PE (black) would raise the pKa and suppress the translocation potential of negatively charged residues (green), which increases the effective positive charge potential of the EMD (+3) thus favoring its retention on the cytoplasmic side of the membrane. Right Panel. In the absence of PE (red) negatively charged residues exert their full translocation potential and result in translocation of the domain that now exhibits a lower effective net positive charge (+1). Even though the charge is still net +1, negatively charged residues may exhibit stronger signals than positively charged residues in the absence of PE. The membrane potential (positive outward) determines EMD directionality. This figure was modified from the original figure published in [85] © Annual Reviews of Biochemistry.