出版社：American Society for Biochemistry and Molecular Biology
摘要：Apolipoprotein E (apoE) is a major protein component of cholesterol-transportinglipoprotein particles in the central nervous system and in plasma.Polymorphisms of apoE are associated with cardiovascular diseaseand with a predisposition to Alzheimer's disease and other formsof neurodegeneration. For full biological activity, apoE mustbe bound to a lipoprotein particle. Complexes of apoE and phospholipidmimic many of these activities. In contrast to a widely accepteddiscoidal model of apoA-I bound to dimyristoylphosphatidylcholine,which is based on solution studies, an X-ray diffraction studyof apoE bound to dipalmitoylphosphatidylcholine (DPPC) indicatedthat apoE•DPPC particles are quasi-spheroidal and thatthe packing of the phospholipid core is similar to a micelle.Using small-angle X-ray scattering, we show that apoE•DPPCparticles in solution are ellipsoidal and that the shape ofthe phospholipid core is compatible with a twisted-bilayer model.The proposed model is consistent with the results of mass spectrometricanalysis of products of limited proteolysis. These revealedthat the nonlipid-bound regions of apoE in the particle areconsistent with an -helical hairpin.Supplementary key words lipoprotein • small-angle X-ray scattering • phospholipid • apolipoprotein A-I
Abbreviations: apo E, apolipoprotein E; DMPC, dimyristoylphosphatidylcholine; DPPC, dipalmitoylphosphatidylcholine; MS/MS, tandem mass spectrometry; ESI, electrospray ionization; POPC, 1-palmitoyl-2-oleoylphosphatidylcholine; SAXS, small-angle X-ray scattering
-helical hairpin.
Supplementary key words lipoprotein • small-angle X-ray scattering • phospholipid • apolipoprotein A-I
Abbreviations: apo E, apolipoprotein E; DMPC, dimyristoylphosphatidylcholine; DPPC, dipalmitoylphosphatidylcholine; MS/MS, tandem mass spectrometry; ESI, electrospray ionization; POPC, 1-palmitoyl-2-oleoylphosphatidylcholine; SAXS, small-angle X-ray scattering
