Role of Lipids in Spheroidal High Density Lipoproteins 英文参考文献.docVIP

RoleofLipidsinSpheroidalHighDensityLipoproteins TimoVuorela1,AndreaCatte1,2,PerttuS.Niemela¨3,AnetteHall1,MarjaT.Hyvo¨nen4 ,Siewert-Jan Marrink5,MikkoKarttunen6,IlpoVattulainen1,7,8* 1DepartmentofPhysics,TampereUniversityofTechnology,Tampere,Finland,2DepartmentofMedicineandCenterforComputationalandStructuralBiology,University ofAlabama,Birmingham,Alabama,UnitedStatesofAmerica,3VTTTechnicalResearchCentreofFinland,Espoo,Finland,4DepartmentofPhysics,UniversityofOulu, Oulu, Finland, 5Groningen Biomolecular Sciences and Biotechnology Institute and Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands, 6Department of Applied Mathematics, The University of Western Ontario, London, Ontario, Canada, 7Department of Applied Physics, Aalto University School of Science and Technology, Espoo, Finland, 8MEMPHYS–Center of Biomembrane Physics, Physics Department, University of Southern Denmark, Odense M, Denmark Abstract Westudythestructureanddynamicsofsphericalhighdensitylipoprotein(HDL)particlesthroughcoarse-grainedmulti- microsecondmoleculardynamicssimulations.WesimulatebothalipiddropletwithouttheapolipoproteinA-I(apoA-I)and thefullHDLparticleincludingtwoapoA-Imoleculessurroundingthelipidcompartment.Thepresentmodelsarethefirst ones among computational studies where the size and lipid composition of HDL are realistic, corresponding to human serumHDL.WefocusontheroleoflipidsinHDLstructureanddynamics.Particularattentionispaidtotheassemblyof lipids and the influence of lipid-protein interactions on HDL properties. We find that the properties of lipids depend significantly on their location in the particle (core, intermediate region, surface). Unlike the hydrophobic core, the intermediate and surface regions are characterized by prominent conformational lipid order. Yet, not only the conformations but also the dynamics of lipids are found to be distinctly different in the different regions of HDL, highlightingtheimportanceofdynamicsinconsider