Cholesterol is found to reside in the center of a polyunsaturated lipid membrane

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Journal titleBiochemistry
Pages70907096; # of pages: 7
AbstractPreviously, we reported neutron diffraction studies on the depth of cholesterol in phosphatidylcholine (PC) bilayers with varying amounts of acyl chain unsaturation [Harroun, T. A., et al. (2006) Biochemistry 45, 1227 1233]. The center of mass of the 2,2,3,4,4,6-D6 deuterated sites on the sterol label was found to reside 16 ? from the middle of the bilayer in 1-palmitoyl-2-oleoylphosphatidylcholine (16:0-18:1PC), 1,2-dioleoylphosphatidylcholine (18:1-18:1PC), and 1-stearoyl-2-arachidonylphosphatidylcholine (18:0-20:4PC). This location places cholesterol s hydroxyl group close to the membrane surface, indicative of the molecule in its commonly understood upright orientation. However, for dipolyunsaturated 20:4-20:4PC membranes the label, thus the hydroxyl group, was found sequestered in the center of the bilayer. We attributed the change in location to the high level of disorder of polyunsaturated fatty acids (PUFA) that is incompatible with proximity to the rigid steroid moiety in its usual upright orientation. From that study, the unresolved question was whether the molecule was inverted or lying flat with respect to the membrane plane, in the middle of the bilayer. We have followed up those results with additional neutron experiments employing [25,26,26,26,27,27-D7]cholesterol, a deuterated analogue labeled in the tail. These diffraction measurements unequivocally show cholesterol lies flat in the middle of 20:4-20:4PC bilayers.
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AffiliationNational Research Council Canada; NRC Canadian Neutron Beam Centre
Peer reviewedNo
NPARC number12338666
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Record identifiera1f04be2-7aaa-4a33-9403-9669e7c711c2
Record created2009-09-10
Record modified2016-05-09
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