Orientation of the headgroup of phosphatidylinositol in a model biomembrane as determined by neutron diffraction.
Derivatives of the sodium salt of dimyristoylphosphatidylinositol (DMPI) have been synthesized specifically deuterated in the headgroup. A 50:50 (molar) mixture of DMPI with dimyristoylphosphatidylcholine (DMPC) hydrated to the level of 16 waters/lipid gives a biomembrane-like Lalpha phase at 50 degrees C. Comparison of the neutron diffraction scattering profiles for deuterated and undeuterated membranes allowed the depth of each deuterium (hydrogen) within the bilayer to be determined to +/-0.5 A. This gave the orientation of the inositol ring which lies more-or-less along the bilayer normal projecting directly out into the water. This orientation is similar to that of the sugar residue in glycolipids and confirms previous models for PI. On the assumption that the (P)O-DAG bond is more-or-less parallel to the bilayer normal, it is consistent with a roughly trans, trans, trans, gauche- conformation for the glyceryl-phosphate-inositol link. In the case of DMPI, it is the C4-hydroxy group which is most fully extended into the water layer, but when this is phosphorylated, the inositol ring turns over and tilts so that the C5-hydroxy group is now the one furthest extended into the water layer. Hence, at each stage in the pathway PI --> PI-4P --> PI-4,5-P2, it is the hydroxy position most exposed to the water which undergoes phosphorylation. Whereas the orientation of the inositol ring in DMPI can be seen simply as maximizing its hydration, the tilt of the ring in DMPI-4P cannot be explained in this way. It is suggested that it is due to an electrostatic interaction.
Bradshaw
J P
JP
Department of Preclinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies, University of Edinburgh, U.K.
Bushby
R J
RJ
Giles
C C
CC
Saunders
M R
MR
D002236:Carbohydrate Conformation; D003903:Deuterium / Q000737:chemistry; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D009502:Neutrons; D016011:Normal Distribution; D010716:Phosphatidylinositols / Q000737:chemistry*; D013696:Temperature; D014961:X-Ray Diffraction
D008051:Lipid Bilayers; D010716:Phosphatidylinositols; C078629:dimyristoylphosphatidylinositol; D003903:Deuterium; D004134:Dimyristoylphosphatidylcholine