Regulation of the membrane insertion and conductance activity of the metamorphic chloride intracellular channel protein CLIC1 by cholesterol

Stella M. Valenzuela, Heba Alkhamici, Louise J. Brown, Oscar C. Almond, Sophia C. Goodchild, Sonia Carne, Paul M G Curmi, Stephen A. Holt, Bruce A. Cornell

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    34 Citations (Scopus)
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    Abstract

    The Chloride Intracellular ion channel protein CLIC1 has the ability to spontaneously insert into lipid membranes from a soluble, globular state. The precise mechanism of how this occurs and what regulates this insertion is still largely unknown, although factors such as pH and redox environment are known contributors. In the current study, we demonstrate that the presence and concentration of cholesterol in the membrane regulates the spontaneous insertion of CLIC1 into the membrane as well as its ion channel activity. The study employed pressure versus area change measurements of Langmuir lipid monolayer films; and impedance spectroscopy measurements using tethered bilayer membranes to monitor membrane conductance during and following the addition of CLIC1 protein. The observed cholesterol dependent behaviour of CLIC1 is highly reminiscent of the cholesterol-dependent-cytolysin family of bacterial pore-forming proteins, suggesting common regulatory mechanisms for spontaneous protein insertion into the membrane bilayer.

    Original languageEnglish
    Article numbere56948
    Pages (from-to)1-8
    Number of pages8
    JournalPLoS ONE
    Volume8
    Issue number2
    DOIs
    Publication statusPublished - 14 Feb 2013

    Bibliographical note

    Copyright the Author(s) 2013. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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