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. 1990 Dec;58(6):1367–1375. doi: 10.1016/S0006-3495(90)82483-8

Primary structure of peptides and ion channels. Role of amino acid side chains in voltage gating of melittin channels.

M T Tosteson 1, O Alvarez 1, W Hubbell 1, R M Bieganski 1, C Attenbach 1, L H Caporales 1, J J Levy 1, R F Nutt 1, M Rosenblatt 1, D C Tosteson 1
PMCID: PMC1281090  PMID: 1703448

Abstract

Melittin produces a voltage-dependent increase in the conductance of planar lipid bilayers. The conductance increases when the side of the membrane to which melittin has been added (cis-side) is made positive. This paper reports observations on the effect of modifying two positively charged amino acid residues within the NH2-terminal region of the molecule: lysine at position 7 (K7), and the NH2-terminal glycine (G1). We have synthesized melittin analogues in which K7 is replaced by asparagine (K7-N), G1 is blocked by a formyl group (G1-f), and in which both modifications of the parent compound were introduced (G1-f, K7-N). The time required to reach peak conductance during a constant voltage pulse was shorter in membranes exposed to the analogues than in membranes modified by melittin. The apparent number of monomers producing a conducting unit for [K7-N]-melittin and [G1-f]-melittin, eight, was found to be greater than the one for [G1-f], K7-N]-melittin and for melittin itself, four. The apparent gating charge per monomer was less for the analogues, 0.5-0.3 than for melittin, one. Essentially similar results were obtained with melittin analogues in which the charge on K7 or G1 or both was blocked by an uncharged N-linked spin label. These results show that the positive charges in the NH2-terminal region of melittin play a major but not exclusive role in the voltage gating of melittin channels in bilayers.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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