Electrostatic Interaction of Globins with Phospholipid Membranes

For the structures of sperm whale myoglobin (swMb), horse heart myoglobin (hhMb), hemoglobin I (HbI) from botfly Gasterophilus intestinalis (giHbI), and monomeric and dimeric hemoglobins HbI and HbII from Lucina pectinata mollusk (lpHbI and lpHbII), roles of electrostatic interactions in stabilization of native conformations of the heme cavity were analyzed, as well as their possible destabilization by interaction with the negatively charged phospholipid membranes. The native conformation of the heme cavity in these globins, both its proximal and distal parts, was shown to be sustained by a system of hydrogen bonds involving the proximal and distal protein residues, the heme propionates, and the nearby polar amino acids on the protein surface (His, Arg, Lys). The hydrogen bond network in the proximal part of the heme pocket controls the position of the Fe atom either outside or within the protoporphyrin plane, which affects the efficiency of ligand binding. In the distal part, the hydrogen bond network formed with the distal protein residue involved (HisE7 in swMb, hhMb, and giHbI and GlnE7 in lpHbII), should stabilize the conformation in which the protein can donate hydrogen to the O2 ligand. The hydrogen bond between the E7 distal residue and O2 ligand prevents rapid dissociation of the latter and plays an important role in the regulation of ligand affinity. The hydrogen bond networks found in the proximal and, especially, in the distal heme environments, must be disrupted when oxyglobin binds to the membrane surface. This disruption caused by interaction of negatively charged phospholipid heads with lysine or arginine residues exposed towards the membrane, altered local pH near the membrane, and the effect of negative electrostatic field of the membrane, can decrease the affinity of the protein for the O2 ligand, thus facilitating its dissociation at the physiological pO2 values in the cell.