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Conductance Studies on Trichotoxin_A50E and Implications for Channel Structure

H. Duclohier ^*, G. M. Alder , C. L. Bashford , H. Brückner , J. K. Chugh ^¶ and B. A. Wallace ^¶

^* Interactions Cellulaires et Moléculaires, UMR 6026 Centre National de la Recherche Scientifique-Université de Rennes I, 35042 Rennes Cedex, France; Department of Biochemistry and Immunology, St. George's Hospital Medical School, Cranmer Terrace, London SW 17 0RE, United Kingdom; Dept. of Food Sciences, Interdisciplinary Research Center, University of Giessen, 35392 Giessen, Germany; and ^¶ Department of Crystallography, Birkbeck College, University of London, London WC1E 7HX, United Kingdom

Correspondence: Address reprint requests to H. Duclohier, E-mail: herve-duclohier{at}wanadoo.fr.

Trichotoxin_A50E is an 18-residue peptaibol whose crystal structure has recently been determined. In this study, the conductance properties of trichotoxin_A50E have been investigated in neutral planar lipid bilayers. The macroscopic current-voltage curves disclose a moderate voltage-sensitivity and the concentration-dependence suggests the channels are primarily hexameric. Under ion gradients, shifts of the reversal potential indicate that cations are preferentially transported. Trichotoxin displays only one single-channel conductance state in a given experiment, but an ensemble of experiments reveals a distribution of conductance levels. This contrasts with the related peptaibol alamethicin, which produces multiple channel levels in a single experiment, indicative of recruitment of additional monomers into different multimeric-sized channels. Based on these conductance measurements and on the recently available crystal structure of trichotoxin_A50E, which is a shorter and straighter helix than alamethicin, a tightly-packed hexameric model structure has been constructed for the trichotoxin channel. It has molecular dimensions and surface electrostatic potential compatible with the observed conductance properties of the most probable and longer-lived channel.