The barrel-stave model as applied to alamethicin and its analogs reevaluated.

Abstract:

:Alamethicin and its analogs from cation selective, multi-conductance channels in lipid bilayers. The conductance levels have been thought to be due to a barrel-stave structure where conducting pores (barrels) are formed by the self-assembly of a variable number of alpha-helical rods (staves). The conductance transitions were then interpreted as the addition or deletion of peptide monomers from the pore-forming complex (Sansom, M.S. 1991. Prog. Biophys. Mol. Biol. 55:139-235). Initially, pore conductances were calculated from that expected of right circular cylinders of "bulk" electrolyte. More recent theories also included the access resistance of the electrolyte outside the pore. However, they all consistently overestimated the observed conductances. The reason for the discrepancy is presented here. Previous theories ignored the effects of ion concentration gradients near the pore. Hence, they only held in the limit of small bilayer potentials (< 25 mV) and so would overestimate measurements that typically used much larger potentials (> 100 mV). This theoretical flaw is corrected by using Läuger's theory of diffusion-limited ion flow (Läuger, P. 1976. Biochim. Biophys. Acta. 455:493-509). Thus, including the effects of ion concentration gradients results in a considerable improvement in predicting pore conductances. It is found that: 1) the effects of ion concentration gradients must be included in the barrel-stave model for it to apply to the available data; 2) previously published explanations for the discrepancy between the model and the data, namely the "distorted bundle" and the "head-to-tail aggregate" hypotheses are not necessary (reviewed by Sansom, 1991).

journal_name

Biophys J

journal_title

Biophysical journal

authors

Laver DR

doi

10.1016/s0006-3495(94)80784-2

subject

Has Abstract

pub_date

1994-02-01 00:00:00

pages

355-9

issue

2 Pt 1

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(94)80784-2

journal_volume

66

pub_type

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