title: Atomic view of calcium-induced clustering of phosphatidylserine in mixed lipid bilayers.
abstract: Membranes play key regulatory roles in biological processes, with bilayer composition exerting marked effects on binding affinities and catalytic activities of a number of membrane-associated proteins. In particular, proteins involved in diverse processes such as vesicle fusion, intracellular signaling cascades, and blood coagulation interact specifically with anionic lipids such as phosphatidylserine (PS) in the presence of Ca(2+) ions. While Ca(2+) is suspected to induce PS clustering in mixed phospholipid bilayers, the detailed structural effects of this ion on anionic lipids are not established. In this study, combining magic angle spinning (MAS) solid-state NMR (SSNMR) measurements of isotopically labeled serine headgroups in mixed lipid bilayers with molecular dynamics (MD) simulations of PS lipid bilayers in the presence of different counterions, we provide site-resolved insights into the effects of Ca(2+) on the structure and dynamics of lipid bilayers. Ca(2+)-induced conformational changes of PS in mixed bilayers are observed in both liposomes and Nanodiscs, a nanoscale membrane mimetic of bilayer patches. Site-resolved multidimensional correlation SSNMR spectra of bilayers containing (13)C,(15)N-labeled PS demonstrate that Ca(2+) ions promote two major PS headgroup conformations, which are well resolved in two-dimensional (13)C-(13)C, (15)N-(13)C, and (31)P-(13)C spectra. The results of MD simulations performed on PS lipid bilayers in the presence or absence of Ca(2+) provide an atomic view of the conformational effects underlying the observed spectra.
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
authors.forename: John M
authors.initials: JM
authors.lastname: Boettcher
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Davis-Harrison
authors.forename: Mary C
authors.initials: MC
authors.lastname: Clay
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Nieuwkoop
authors.forename: Y Zenmei
authors.initials: YZ
authors.lastname: Ohkubo
authors.forename: Emad
authors.initials: E
authors.lastname: Tajkhorshid
authors.forename: James H
authors.initials: JH
authors.lastname: Morrissey
authors.forename: Chad M
authors.initials: CM
authors.lastname: Rienstra
mesh_terms: D002118:Calcium / Q000494:pharmacology*; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D009068:Movement / Q000187:drug effects; D049329:Nanostructures / Q000737:chemistry; D044367:Phase Transition / Q000187:drug effects; D010718:Phosphatidylserines / Q000737:chemistry* / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology
chemical_list: D008051:Lipid Bilayers; D010718:Phosphatidylserines; D012964:Sodium; D002118:Calcium