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Am J Physiol. 1997 Dec;273(6 Pt 1):C1925-36.

Histone-induced damage of a mammalian epithelium: the role of protein and membrane structure.

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Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77555, USA.


In a previous report [T. J. Kleine, A. Gladfelter, P. N. Lewis, and S. A. Lewis, Am. J. Physiol. 268 (Cell Physiol. 37): C1114-C1125, 1995], we found that the cationic DNA-binding proteins histones H4, H1, and H5 caused a voltage-dependent increase in the transepithelial conductance in rabbit urinary bladder epithelium. In this study, results from lipid bilayer experiments suggest that histones H5-H1 and H4 form variably sized conductive units. Purified fragments of histones H4 and H5 were used to determine the role of histone tertiary structure in inducing conductance. Isolated COOH- and NH2-terminal tails of histone H4, which are random coils, were inactive, whereas the central alpha-helical domain induced a conductance increase. Although the activities of the central fragment and intact histone H4 were in many ways similar, the dose-response relationships suggest that the isolated central domain was much less potent than intact histone H4. This suggests than the NH2- and COOH-terminal tails are also important for histone H4 activity. For histone H5, the isolated globular central domain was inactive. Thus the random-coil NH2- and COOH-terminal tails are important for H5 activity as well. These results indicate that histone molecules interact directly with membrane phospholipids to form a channel and that protein tertiary structure and the degree of positive charge play an important role in this activity.

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