Wednesday, May 10, 2006
JACS - Volume 128, Issue 16
Cory's Comment: Using 2H SSNMR to determine the orientation of cholesterol in membranes as a function of chain unsaturation.
Title: Molecular Organization of Cholesterol in Unsaturated Phosphatidylethanolamines: X-ray Diffraction and Solid State 2H NMR Reveal Differences with Phosphatidylcholines
Authors: Saame Raza Shaikh, Vadim Cherezov, Martin Caffrey, Smita P. Soni, Daniel LoCascio, William Stillwell, and Stephen R. Wassall
Page #: 5375
Abstract: The major mammalian plasma membrane lipids are phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and cholesterol. Whereas PC-cholesterol interactions are well studied, far less is known about those between PE and cholesterol. Here, we investigated the molecular organization of cholesterol in PEs that vary in their degree of acyl chain unsaturation. For heteroacid sn-1 saturated (palmitoyl), sn-2 unsaturated (various acyl chain) PEs, cholesterol solubility determined by X-ray diffraction was essentially identical with 1 (oleoyl, 51 ± 3 mol %) and 2 (linoleoyl, 49 ± 2 mol %) double bonds before decreasing progressively with 4 (arachidonyl, 41 ± 3 mol %) and 6 (docosahexaenoyl, 31 ± 3 mol %) double bonds. With 6 double bonds in each chain, cholesterol solubility was further reduced to 8.5 ± 1 mol %. However, 2H NMR experiments established that the orientation of cholesterol in the same heteroacid PE membranes was unaffected by the degree of acyl chain unsaturation. A tilt angle of 15 ± 1 was measured when equimolar [3-2H1]cholesterol was added, regardless of the number of double bonds in the sn-2 chain. The finding that solubility of cholesterol in sn-1 saturated PEs depends on the amount of polyunsaturation in the sn-2 chain of PE differs from the equivalent PCs that universally incorporate ~50 mol % sterol. Unlike PCs, a differential in affinity for cholesterol and tendency to drive lateral segregation is inferred between polyunsaturated PEs. This distinction may have biological implications reflected by the health benefits of dietary polyunsaturated fatty acids that are often taken up into PE > PC.