Arabidopsis accelerated cell death 11, ACD11, Is a ceramide-1-phosphate transfer protein and intermediary regulator of phytoceramide levels

Dhirendra K. Simanshu, Xiuhong Zhai, David Munch, Daniel Hofius, Jonathan E. Markham, Jacek Bielawski, Alicja Bielawska, Lucy Malinina, Julian G. Molotkovsky, John W. Mundy, Dinshaw J. Patel, Rhoderick E. Brown

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45 Scopus citations

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 invivo 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.

Original languageEnglish (US)
Pages (from-to)388-399
Number of pages12
JournalCell reports
Volume6
Issue number2
DOIs
StatePublished - 2014

Bibliographical note

Funding Information:
This research was supported by NIH/NIGMS GM45928 (to R.E.B.), NIH/NCI CA121493 (to D.J.P. and R.E.B.), Danish Strategic Research Council 09-067148 (to J.W.M.), NSF/MCB 0843312 (to J.E.M.), NIH/NCRR C06 RR018823 (to J.B. and A.B.), Spanish Ministerio de Ciencia e Innovacion BFU2010-17711 (to L.M.), Russian Foundation for Basic Research #12-04-00168 (to J.G.M.), Hormel Foundation (to R.E.B.), Abby Rockefeller Mauze Trust (to D.J.P.), and Maloris Foundation (to D.J.P.). We thank J. Peter Slotte (Åbo Akademi University) for the IPC lipid, Helen Pike (UMN-Hormel Institute) for purifying protein used for transfer activity analyses, and the staff of X-29 beamline at the National Synchrotron Light Source and ID-24-C/E beamlines at the Advanced Photon Source for help. The Lipidomics Shared Resource MUSC is partially supported by P30 CA138313, HCC, and P20 RR017677 SC COBRE in Lipidomics and Pathobiology.

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