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Science 27 May 1988:
Vol. 240. no. 4856, pp. 1177 - 1181
DOI: 10.1126/science.2453923
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Articles

Science, Vol 240, Issue 4856, 1177-1181
Copyright © 1988 by American Association for the Advancement of Science

articles

Synthetic amphiphilic peptide models for protein ion channels

JD Lear, ZR Wasserman, and WF DeGrado

Central Research and Development Department, E. I. du Pont de Nemours and Company, Wilmington, DE 19898.

Ion channel proteins are important for the conduction of ions across biological membranes. Recent analyses of their sequences have suggested that they are composed of bundles of alpha-helices that associate to form ion-conducting channels. To gain insight into the mechanisms by which alpha-helices can aggregate and conduct ions, three model peptides containing only leucine and serine residues were synthesized and characterized. A 21-residue peptide, H2N-(Leu-Ser-Ser-Leu-Leu-Ser-Leu)3-CONH2, which was designed to be a membrane-spanning amphiphilic alpha-helix, formed well-defined ion channels with ion permeability and lifetime characteristics resembling the acetylcholine receptor. In contrast, a 14-residue version of this peptide, which was too short to span the phospolipid bilayer as an alpha-helix, failed to form discrete, stable channels. A third peptide, H2N-(Leu-Ser-Leu-Leu-Leu-Ser-Leu)3-CONH2, in which one serine per heptad repeat was replaced by leucine, produced proton-selective channels. Computer graphics and energy minimization were used to create molecular models that were consistent with the observed properties of the channels.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)