title: Phosphatidylserine Stimulates Ceramide 1-Phosphate (C1P) Intermembrane Transfer by C1P Transfer Proteins.
abstract: Genetic models for studying localized cell suicide that halt the spread of pathogen infection and immune response activation in plants includeArabidopsis accelerated-cell-death 11mutant (acd11). In this mutant, sphingolipid homeostasis is disrupted via depletion of ACD11, a lipid transfer protein that is specific for ceramide 1-phosphate (C1P) and phyto-C1P. The C1P binding site in ACD11 and in human ceramide-1-phosphate transfer protein (CPTP) is surrounded by cationic residues. Here, we investigated the functional regulation of ACD11 and CPTP by anionic phosphoglycerides and found that 1-palmitoyl-2-oleoyl-phosphatidic acid or 1-palmitoyl-2-oleoyl-phosphatidylglycerol (≤15 mol %) in C1P source vesicles depressed C1P intermembrane transfer. By contrast, replacement with 1-palmitoyl-2-oleoyl-phosphatidylserine stimulated C1P transfer by ACD11 and CPTP. Notably, "soluble" phosphatidylserine (dihexanoyl-phosphatidylserine) failed to stimulate C1P transfer. Also, none of the anionic phosphoglycerides affected transfer action by human glycolipid lipid transfer protein (GLTP), which is glycolipid-specific and has few cationic residues near its glycolipid binding site. These findings provide the first evidence for a potential phosphoglyceride headgroup-specific regulatory interaction site(s) existing on the surface of any GLTP-fold and delineate new differences between GLTP superfamily members that are specific for C1Pversusglycolipid.
authors.affiliation: From the Hormel Institute, University of Minnesota, Austin, Minnesota 55912, zhai@hi.umn.edu.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Zhai
authors.affiliation: From the Hormel Institute, University of Minnesota, Austin, Minnesota 55912.
authors.forename: Yong-Guang
authors.initials: YG
authors.lastname: Gao
authors.affiliation: From the Hormel Institute, University of Minnesota, Austin, Minnesota 55912.
authors.forename: Shrawan K
authors.initials: SK
authors.lastname: Mishra
authors.affiliation: the Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065.
authors.forename: Dhirendra K
authors.initials: DK
authors.lastname: Simanshu
authors.affiliation: the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Boldyrev
authors.affiliation: the Medical Genomic Facility-Proteomics Core, Mayo Foundation, Rochester, Minnesota 55905, and.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Benson
authors.affiliation: the Medical Genomic Facility-Proteomics Core, Mayo Foundation, Rochester, Minnesota 55905, and.
authors.forename: H Robert
authors.initials: HR
authors.lastname: Bergen
authors.affiliation: From the Hormel Institute, University of Minnesota, Austin, Minnesota 55912.
authors.forename: Lucy
authors.initials: L
authors.lastname: Malinina
authors.affiliation: the Department of Biology, BioCenter, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: John
authors.initials: J
authors.lastname: Mundy
authors.affiliation: the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
authors.forename: Julian G
authors.initials: JG
authors.lastname: Molotkovsky
authors.affiliation: the Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065.
authors.forename: Dinshaw J
authors.initials: DJ
authors.lastname: Patel
authors.affiliation: From the Hormel Institute, University of Minnesota, Austin, Minnesota 55912, reb@umn.edu.
authors.forename: Rhoderick E
authors.initials: RE
authors.lastname: Brown
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000737:chemistry / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002518:Ceramides / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D010718:Phosphatidylserines / Q000502:physiology*; D049294:Phospholipid Transfer Proteins; D011485:Protein Binding; D055672:Static Electricity
chemical_list: C451029:ACD11 protein, Arabidopsis; D051017:Apoptosis Regulatory Proteins; D029681:Arabidopsis Proteins; C583333:CPTP protein, human; D002352:Carrier Proteins; D002518:Ceramides; D026901:Membrane Transport Proteins; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; C065576:ceramide 1-phosphate
keywords: Arabidopsis thaliana; lipid trafficking; lipid-protein interaction; membrane biophysics; phosphatidic acid; phosphatidylglycerol; phosphatidylserine; protein-lipid interaction; sphingolipid