Interaction of amphiphiles with integral membrane proteins. II. A simple, minimal model for the nonspecific interaction of amphiphiles with the anion exchanger of the erythrocyte membrane.
In a previous paper we have reported on the structural perturbation of the erythrocyte membrane anion exchanger by a regular series of model amphiphiles, as shown by differential scanning calorimetry (Gruber, H.J. and Low, P.S., Biochim. Biophys. Acta, preceding article). Now the data are interpreted by a model in which the effects of amphiphile structure upon buffer-membrane partitioning are well separated from the dependence of the intrinsic potencies of membrane-bound amphiphiles upon amphiphile structure. The buffer-membrane partitioning situation was demonstrated to regularly change between extremes within a series of homologous amphiphiles, i.e. from a negligible to a predominant fraction of total amphiphile in the sample residing in the membrane. Based upon this demonstration a large number of reports on the chain length dependence of apparent potency could be reinterpreted in terms of chain length profiles of intrinsic potency, allowing for a comparison of the responses of various membrane proteins to homologous series of amphiphiles. The response patterns for chain length variation could be divided into three distinct classes: the intrinsic potency (i) can be independent of chain length over a very wide range of length, (ii) it can be rather independent up to a critical length where a sudden cut-off in potency occurs, or (iii) it can drop monotonically over a wide range of chain length. The intrinsic potency values of saturated fatty acids in destabilizing the anion exchanger were interpreted by very simple assumptions: only direct interactions between amphiphiles and target proteins and a simple amphiphile partition equilibrium between a pool of equivalent low affinity sites on the protein and the bulk lipid matrix. The observed monotonic decay of the intrinsic potency of saturated fatty acids with increasing chain length from C8 to C20 was translated into a constant increment of free energy by which each additional CH2 favors the transfer away from sites on the protein towards the bulk lipid matrix. Arguments were presented suggesting that the direct interaction between amphiphiles and target protein is completely nonspecific for alkyl chain length while the residual specificity for shorter over longer amphiphiles is due to the higher tendency of longer chains to preferentially bind in the bulk lipid matrix. Thus a completely new role of the lipid as a competitor, rather than a mediator, was postulated.
Gruber
H J
HJ
Department of Chemistry, Purdue University, West Lafayette, IN.
D002462:Cell Membrane / Q000502:physiology*; D005227:Fatty Acids; D006801:Humans; D066298:In Vitro Techniques; D008563:Membrane Lipids / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D008962:Models, Theoretical; D011489:Protein Denaturation; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D005227:Fatty Acids; D008563:Membrane Lipids; D008565:Membrane Proteins