Conformational changes of adrenocorticotropin peptides upon interaction with lipid membranes revealed by infrared attenuated total reflection spectroscopy

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Abstract
IR attenuated total reflection (IR-ATR) spectroscopy was used to study conformational and topological aspects of the interaction between 2 ACTH fragments and dioleoylphosphatidylcholine membranes. Corticotropin-(1-10)-decapeptide, ACTH1-10, existed as a rigid antiparallel pleated sheet structure in dry membranes. In aqueous environment, it completely escaped from the lipid. This dominant preference for the aqueous phase is a possible explanation for the very low biological potency of ACTH1-10 in some assays. The very potent corticotropin-(1-24)-tetracosapeptide, ACTH1-24, was firmly incorporated into dry and wet membrane. Aqueous environment even promoted the peptide-lipid interaction. Under these latter conditions, part of the molecule entered the bilayer and adopted a helical structure with the axis oriented perpendicularly to the bilayer plane. Contact of a 0.1 mM solution of ACTH1-24 in liquid deuterium oxide with the pure lipid membrane system resulted in measurable adsorption of the peptide to the membrane with the same conformational and topological characteristics as described above (perpendicularly oriented helix entering the bilayer). The helical part of the ACTH1-24 molecule entering the bilayer was the quite hydrophobic N-terminal decapeptide unit (message segment). The adjacent hydrophilic C-terminal tetradecapeptide unit (address segment) remained on the membrane surface. As the message region is essential for triggering corticotropin receptors, its intrusion into the membrane and its adoption of an oriented, helical conformation may facilitate receptor stimulation. The observed specific membrane interaction critically depended on the presence of the address segment. This could explain the potentiating effect of the address in pharmacological experiments.