Electrostatic binding of proteins to membranes. Theoretical predictions and experimental results with charybdotoxin and phospholipid vesicles.

We previously applied the Poisson-Boltzmann equation to atomic models of phospholipid bilayers and basic peptides to calculate their electrostatic interactions from first principles (Ben-Tal, N., B. Honig, R. M. Peitzsch, G. Denisov, and S. McLaughlan. 1996. Binding of small basic peptides to membranes containing acidic lipids. Theoretical models and experimental results. Biophys. J. 71:561-575). Specifically, we calculated the molar partition coefficient, K (the reciprocal of the lipid concentration at which 1/2 the peptide is bound), of simple basic peptides (e.g., pentalysine) with phospholipid vesicles. The theoretical predictions agreed well with experimental measurements of the binding, but the agreement could have been fortuitous because the structure(s) of these flexible peptides is not known. Here we use the same theoretical approach to calculate the membrane binding of two small proteins of known structure: charybdotoxin (CTx) and iberiotoxin (IbTx); we also measure the binding of these proteins to phospholipid vesicles. The theoretical model describes accurately the dependence of K on the ionic strength and mol % acidic lipid in the membrane for both CTx (net charge +4) and IbTx (net charge +2). For example, the theory correctly predicts that the value of K for the binding of CTx to a membrane containing 33% acidic lipid should decrease by a factor of 10(5) when the salt concentration increases from 10 to 200 mM. We discuss the limitations of the theoretical approach and also consider a simple extension of the theory that incorporates nonpolar interactions.