title: Arabidopsis accelerated cell death 11, ACD11, is a ceramide-1-phosphate transfer protein and intermediary regulator of phytoceramide levels.
abstract: The accelerated cell death 11 (acd11) mutant of Arabidopsis provides a genetic model for studying immune response activation and localized cellular suicide that halt pathogen spread during infection in plants. Here, we elucidate ACD11 structure and function and show that acd11 disruption dramatically alters the in vivo balance of sphingolipid mediators that regulate eukaryotic-programmed cell death. In acd11 mutants, normally low ceramide-1-phosphate (C1P) levels become elevated, but the relatively abundant cell death inducer phytoceramide rises acutely. ACD11 exhibits selective intermembrane transfer of C1P and phyto-C1P. Crystal structures establish C1P binding via a surface-localized, phosphate headgroup recognition center connected to an interior hydrophobic pocket that adaptively ensheaths lipid chains via a cleft-like gating mechanism. Point mutation mapping confirms functional involvement of binding site residues. A π helix (π bulge) near the lipid binding cleft distinguishes apo-ACD11 from other GLTP folds. The global two-layer, α-helically dominated, "sandwich" topology displaying C1P-selective binding identifies ACD11 as the plant prototype of a GLTP fold subfamily.
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Dhirendra K
authors.initials: DK
authors.lastname: Simanshu
authors.affiliation: Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Zhai
authors.affiliation: Department of Biology, BioCenter, University of Copenhagen, 2200 Copenhagen N, Denmark.
authors.forename: David
authors.initials: D
authors.lastname: Munch
authors.affiliation: Department of Biology, BioCenter, University of Copenhagen, 2200 Copenhagen N, Denmark.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hofius
authors.affiliation: Department of Biochemistry, University of Nebraska, N146 Beadle Center, Lincoln, NE 68588, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Markham
authors.affiliation: Department of Biochemistry and Molecular Biology, Lipidomics Shared Resource Mass Spectrometry Lab, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Jacek
authors.initials: J
authors.lastname: Bielawski
authors.affiliation: Department of Biochemistry and Molecular Biology, Lipidomics Shared Resource Mass Spectrometry Lab, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Alicja
authors.initials: A
authors.lastname: Bielawska
authors.affiliation: Structural Biology Unit, CIC bioGUNE, Technology Park of Bizkaia, 48160 Derio-Bilbao, Spain.
authors.forename: Lucy
authors.initials: L
authors.lastname: Malinina
authors.affiliation: 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: Department of Biology, BioCenter, University of Copenhagen, 2200 Copenhagen N, Denmark. Electronic address: mundy@science.ku.dk.
authors.forename: John W
authors.initials: JW
authors.lastname: Mundy
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. Electronic address: pateld@mskcc.org.
authors.forename: Dinshaw J
authors.initials: DJ
authors.lastname: Patel
authors.affiliation: Hormel Institute, University of Minnesota, Austin, MN 55912, USA. Electronic address: reb@umn.edu.
authors.forename: Rhoderick E
authors.initials: RE
authors.lastname: Brown
mesh_terms: D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism*; D029681:Arabidopsis Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002518:Ceramides / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding
chemical_list: C451029:ACD11 protein, Arabidopsis; D051017:Apoptosis Regulatory Proteins; D029681:Arabidopsis Proteins; D002518:Ceramides; D026901:Membrane Transport Proteins; C065576:ceramide 1-phosphate