Arabidopsis Accelerated Cell Death 11, ACD11, Is a Ceramide-1-Phosphate Transfer Protein and Intermediary Regulator of Phytoceramide Levels

Authors

Dhirendra K. Simanshu, Memorial Sloan-Kettering Cancer Center
Xiuhong Zhai, University of Minnesota
David Munch, University of Coppenhagen
Daniel Hofius, Swedish University of Agricultural Sciences
Jennifer E. Markham, University of Nebraska-LincolnFollow
Jacek Bielawski, Medical University of South Carolina
Alicja Bielawska, Medical University of South Carolina
Lucy Malinina, CIC bioGUNE
Julian G. Molotkovsky, Russian Academy of Sciences
John W. Mundy, University of CopenhagenFollow
Dinshaw J. Patel, Memorial Sloan-Kettering Cancer CenterFollow
Rhoderick E. Brown, University of MinnesotaFollow

Document Type

Article

Date of this Version

1-30-2014

Citation

Cell Reports (January 30, 2014) 6: 388–399

doi: 10.1016/j.celrep.2013.12.023

Comments

Copyright 2014, the authors

Open access material

License: Creative Commons Attribution-NanCommercial-NoDerivatives (CC BY-NC-ND)

http://dx.doi.org/10.1016/j.celrep.2013.12.023

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.