Document Detail


Alpha-helical hydrophobic polypeptides form proton-selective channels in lipid bilayers.
MedLine Citation:
PMID:  7520289     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Proton translocation is important in membrane-mediated processes such as ATP-dependent proton pumps, ATP synthesis, bacteriorhodopsin, and cytochrome oxidase function. The fundamental mechanism, however, is poorly understood. To test the theoretical possibility that bundles of hydrophobic alpha-helices could provide a low energy pathway for ion translocation through the lipid bilayer, polyamino acids were incorporated into extruded liposomes and planar lipid membranes, and proton translocation was measured. Liposomes with incorporated long-chain poly-L-alanine or poly-L-leucine were found to have proton permeability coefficients 5 to 7 times greater than control liposomes, whereas short-chain polyamino acids had relatively little effect. Potassium permeability was not increased markedly by any of the polyamino acids tested. Analytical thin layer chromatography measurements of lipid content and a fluorescamine assay for amino acids showed that there were approximately 135 polyleucine or 65 polyalanine molecules associated with each liposome. Fourier transform infrared spectroscopy indicated that a major fraction of the long-chain hydrophobic peptides existed in an alpha-helical conformation. Single-channel recording in both 0.1 N HCl and 0.1 M KCl was also used to determine whether proton-conducting channels formed in planar lipid membranes (phosphatidylcholine/phosphatidylethanolamine, 1:1). Poly-L-leucine and poly-L-alanine in HCl caused a 10- to 30-fold increase in frequency of conductive events compared to that seen in KCl or by the other polyamino acids in either solution. This finding correlates well with the liposome observations in which these two polyamino acids caused the largest increase in membrane proton permeability but had little effect on potassium permeability. Poly-L-leucine was considerably more conductive than poly-L-alanine due primarily to larger event amplitudes and, to a lesser extent, a higher event frequency. Poly-L-leucine caused two populations of conductive events, one in the 0.1-0.5 pA range, and one in the 1.0-5.0 pA range, whereas nearly all events caused by poly-L-alanine were in the 0.1-0.5 pA range at an applied voltage of +60 mV. The channel-like activity appeared to switch between conductive and nonconductive states, with most open-times in the range of 50-200 ms. We conclude that hydrophobic polyamino acids produce proton-conducting defects in lipid bilayers that may be used to model functional proton channels in biological membranes.
Authors:
A E Oliver; D W Deamer
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Biophysical journal     Volume:  66     ISSN:  0006-3495     ISO Abbreviation:  Biophys. J.     Publication Date:  1994 May 
Date Detail:
Created Date:  1994-09-21     Completed Date:  1994-09-21     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370626     Medline TA:  Biophys J     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1364-79     Citation Subset:  IM; S    
Affiliation:
Section of Molecular and Cellular Biology, University of California-Davis 95616.
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MeSH Terms
Descriptor/Qualifier:
Alamethicin / chemistry
Biophysical Phenomena
Biophysics
Electric Conductivity
Gramicidin / chemistry
Ion Channels / chemistry*
Lipid Bilayers / chemistry*
Liposomes / chemistry
Membrane Potentials
Models, Molecular
Peptides / chemistry*
Permeability
Protein Structure, Secondary
Protons
Spectroscopy, Fourier Transform Infrared
Chemical
Reg. No./Substance:
0/Ion Channels; 0/Lipid Bilayers; 0/Liposomes; 0/Peptides; 0/Protons; 1405-97-6/Gramicidin; 25191-17-7/polyalanine; 25248-98-0/polyleucine; 27061-78-5/Alamethicin
Investigator
Investigator/Affiliation:
D W Deamer / U CA, Santa Cruz
Comments/Corrections

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