Membrane protein-lipid hydrogen bonding: evidence from protein kinase C, diglyceride, and tumor promotors

Membrane-bound proteins owe their retention and conformation in the lipid bilayer to hydrophobic peptide domains. Additional fixation, by protein-lipid hydrogen bonding, has been suggested, and recent reports on protein kinase C activation by diacylglycerol (DG) provide an unambiguous model for such bonding. The sn-1,2-diacylglycerol appears to donate a hydrogen bond from the sn-3 hydroxyl to the enzyme and to receive two hydrogen bonds, in the sn-1 and sn-2 ester CO groups, from the enzyme. This arrangement is confirmed in phorbol ester, a competitive inhibitor of DG for the kinase. This tumor promotor has a nearly identical spatial arrangement of hydrogen bond donor (9 alpha-OH) and acceptors (12 and 13 ester CO); so have two other tumor promotors, teleocidin and aplysiatoxin. There are reasons to believe that protein kinase C is not the only protein that is bound to membrane lipids by hydrogen bonding, and such bonding will have to be considered in membrane-associated events such as fusion, cross-membrane transport, or anesthesia.