Does the binding of clusters of basic residues to acidic lipids induce domain formation in membranes?
Several proteins that are important components of the calcium/phospholipid second messenger system (e.g. phospholipase C, protein kinase C, myristoylated alanine-rich C kinase substrate (MARCKS) and pp60src) contain clusters of basic residues that can interact with acidic lipids on the cytoplasmic surface of plasma membranes. We have studied the membrane binding of MARCKS and pp60src, peptides that mimic the basic regions of these proteins, and simple model peptides. Specifically, we determined how the binding of these model peptides depends on (1) the number of basic residues in the peptide (2) the fraction of acidic lipids in the membrane (3) the ionic strength of the solution (4) the chemical nature of the basic residues (Arg versus Lys) and the acidic phospholipids [phosphatidylglycerol (PG) versus phosphatidylserine (PS)] (5) the pressure and (6) the temperature. The results are consistent with a simple theoretical model: each basic residue in a peptide binds independently to an acidic lipid with an intrinsic microscopic association constant of 1-10 M-1 (binding energy congruent to 1 kcal/mol). The binding is described with a mass action formalism and the non-specific electrostatic accumulation of the peptides in the aqueous diffuse double layer is described with the Gouy-Chapman theory. This Gouy-Chapman/mass action model accounts surprisingly well for the sigmoidal dependence of binding on the percentage of acidic lipids in the membrane (apparent co-operativity or Hill coefficient > 1); the model assumes that the multivalent basic peptides bind > 1 acidic lipids and thus induce or stabilize domain formation.
Buser
C A
CA
Department of Physiology and Biophysics, HSC, SUNY, Stony Brook, NY 11790, USA.
Kim
J
J
McLaughlin
S
S
Peitzsch
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
D008563:Membrane Lipids; D011506:Proteins