Bax, despite being a cytosolic protein, has the distinct ability to form channels in the mitochondrial outer membrane, which are capable of releasing proteins that initiate the execution phase of apoptosis. When studied in a planar phospholipid membrane system, full-length activated Bax can form conducting entities consistent with linearly organized three-channel units displaying steep voltage-gating (n=14) that rivals that of channels in excitable membranes. In addition, the channels display strong positive co-operativity possibly arising from the charge distribution of the voltage sensors. On the basis of functional behaviour, one of the channels in this functional triplet is oriented in the opposite direction to the others often resulting in conflicts between the effects of the electric field and the positive co-operativity of adjacent channels. The closure of the first channel occurs at positive potentials and this permits the second to close, but at negative potentials. The closure of the second channel in turn permits closure of the third, but at positive potentials. Positive co-operativity manifests itself in a number of ways including the second and the third channels opening virtually simultaneously. This extraordinary behaviour must have important, although as yet undefined, physiological roles.
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Research Article|
March 28 2014
Bax channel triplet: co-operativity and voltage gating
Shang H. Lin;
Shang H. Lin
*Department of Biology, University of Maryland, College Park, MD 20742, U.S.A.
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Nuval Cherian;
Nuval Cherian
*Department of Biology, University of Maryland, College Park, MD 20742, U.S.A.
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Benjamin Wu;
Benjamin Wu
*Department of Biology, University of Maryland, College Park, MD 20742, U.S.A.
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Hyo Phee;
Hyo Phee
*Department of Biology, University of Maryland, College Park, MD 20742, U.S.A.
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Christy Cho;
Christy Cho
*Department of Biology, University of Maryland, College Park, MD 20742, U.S.A.
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Marco Colombini
Marco Colombini
1
*Department of Biology, University of Maryland, College Park, MD 20742, U.S.A.
1To whom correspondence should be addressed (email colombini@umd.edu).
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Publisher: Portland Press Ltd
Received:
October 31 2013
Revision Received:
January 14 2014
Accepted:
February 06 2014
Accepted Manuscript online:
February 06 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 459 (2): 397–404.
Article history
Received:
October 31 2013
Revision Received:
January 14 2014
Accepted:
February 06 2014
Accepted Manuscript online:
February 06 2014
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Citation
Shang H. Lin, Nuval Cherian, Benjamin Wu, Hyo Phee, Christy Cho, Marco Colombini; Bax channel triplet: co-operativity and voltage gating. Biochem J 15 April 2014; 459 (2): 397–404. doi: https://doi.org/10.1042/BJ20131441
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