Involvement of nonlamellar-prone lipids in the stability increase of human cytochrome P450 1A2 in reconstituted membranes

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Title
Involvement of nonlamellar-prone lipids in the stability increase of human cytochrome P450 1A2 in reconstituted membranes
Author(s)
T Ahn; C H Yun; Doo-Byoung Oh
Bibliographic Citation
Biochemistry, vol. 44, no. 25, pp. 9188-9196
Publication Year
2005
Abstract
The effect of nonlamellar-prone lipids, diacylglycerol (DG) and phosphatidylethanolamine (PE), on the stability of human cytochrome P450 1A2 (CYP1A2) was examined. When 100% phosphatidylcholine (PC) in standard vesicles was gradually replaced with either DG or PE, the stability of CYP1A2 increased; the incubation time-dependent destruction of spectrally detectable P450, decrease of catalytic activity, reduction of intrinsic fluorescence, and increased sensitivity to trypsin digestion were significantly alleviated. The ternary system of PC/PE/DG increased the stability of CYP1 A2 more, even at lower concentrations of each nonlamellar-prone lipid, than that of the binary lipid mixture (PC/nonlamellar lipid). By incorporating the nonlamellar-prone lipids, the CYP1A2-induced increase of the surface pressure of the lipid monolayer was much higher compared to that for 100% PC. Increased surface pressure indicates a deep insertion of the protein into lipid monolayers. Nonlamellar lipids also increased the transition temperature of CYP1A2 in thermal unfolding and reduced the incubation time-dependent detachment of membrane-bound CYP1A2 from vesicles. Taken together, these results suggest that nonlamellar lipids per se and/or the phase properties of the membrane containing these lipids are important in the enhanced stability of CYP1A2 and the concomitant maintenance of catalytic activity of the protein.
ISSN
0006-2960
Publisher
Amer Chem Soc
DOI
http://dx.doi.org/10.1021/bi050051e
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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