An electrostatic/hydrogen bond switch as the basis for the specific interaction of phosphatidic acid with proteins.
Phosphatidic acid (PA) is a minor but important phospholipid that, through specific interactions with proteins, plays a central role in several key cellular processes. The simple yet unique structure of PA, carrying just a phosphomonoester head group, suggests an important role for interactions with the positively charged essential residues in these proteins. We analyzed by solid-state magic angle spinning 31P NMR and molecular dynamics simulations the interaction of low concentrations of PA in model membranes with positively charged side chains of membrane-interacting peptides. Surprisingly, lysine and arginine residues increase the charge of PA, predominantly by forming hydrogen bonds with the phosphate of PA, thereby stabilizing the protein-lipid interaction. Our results demonstrate that this electrostatic/hydrogen bond switch turns the phosphate of PA into an effective and preferred docking site for lysine and arginine residues. In combination with the special packing properties of PA, PA may well be nature's preferred membrane lipid for interfacial insertion of positively charged membrane protein domains.
Kooijman
Edgar E
EE
Department Biochemistry of Membranes, Bijvoet Center, Institute of Biomembranes, Utrecht University, Utrecht 3584 CH, The Netherlands. e.e.kooijman@gmail.com
Tieleman
D Peter
DP
Testerink
Christa
C
Munnik
Teun
T
Rijkers
Dirk T S
DT
Burger
Koert N J
KN
de Kruijff
Ben
B
D024361:Amino Acids, Basic / Q000737:chemistry; D003198:Computer Simulation; D006860:Hydrogen Bonding; D007477:Ions / Q000737:chemistry; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D010712:Phosphatidic Acids / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity
D024361:Amino Acids, Basic; D007477:Ions; D008081:Liposomes; D010455:Peptides; D010712:Phosphatidic Acids; D011506:Proteins