Membrane lipid phase as catalyst for peptide-receptor interactions.

AUTOR(ES)

Sargent, D F

RESUMO

Catalysis of ligand-receptor interactions is proposed as an important function of the lipid phase of the cell membrane. The catalytic mechanism is deduced from observed specific interactions of amphiphilic peptides with artificial lipid bilayers. In our model a direct ligand-receptor reaction is replaced by multiple sequential steps including surface accumulation of charged ligands, ligand-membrane interactions, and ultimately binding to the receptor itself. By dividing the total free energy of binding among several steps, the energy per step, including the intrinsic receptor interaction energy, is kept to moderate values. The model thereby yields simple explanations for the large apparent association constants, the high association and dissociation rates, and the heterogeneity of binding sites so frequently found with pharmacological and biochemical ligand-receptor interactions. Furthermore, the measured apparent association constant is a function of the whole system rather than just the receptor. The same, fully functional receptor may show different binding characteristics in different surroundings, such as in another tissue or in a reconstituted system.

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