4NT2

Crystal structure of Arabidopsis ACD11 (accelerated-cell-death 11) complexed with lyso-sphingomyelin (d18:1) at 2.4 Angstrom resolution

Summary for 4NT2

• Entry DOI: 10.2210/pdb4nt2/pdb
• Related: 4NT1 4NTG 4NTI 4NTO
• Descriptor: accelerated-cell-death 11, 2-{[(R)-{[(2S,3R,4E)-2-amino-3-hydroxyoctadec-4-en-1-yl]oxy}(hydroxy)phosphoryl]oxy}-N,N,N-trimethylethanaminium, SULFATE ION, ... (5 entities in total)
• Functional Keywords: protein-lipid complexes, gltp-fold, lipid transfer protein, cell death, lysosm, lysosphingomyelin, ceramide-1-phosphate, c1p, transport protein
• Biological source: Arabidopsis thaliana (mouse-ear cress)
• Cellular location: Cytoplasm : O64587
• Total number of polymer chains: 1
• Total formula weight: 24333.18

Authors

Simanshu, D.K.,Brown, R.E.,Patel, D.J. (deposition date: 2013-11-29, release date: 2014-02-05, Last modification date: 2023-09-20)

Primary citation

Simanshu, D.K.,Zhai, X.,Munch, D.,Hofius, D.,Markham, J.E.,Bielawski, J.,Bielawska, A.,Malinina, L.,Molotkovsky, J.G.,Mundy, J.W.,Patel, D.J.,Brown, R.E.
Arabidopsis Accelerated Cell Death 11, ACD11, Is a Ceramide-1-Phosphate Transfer Protein and Intermediary Regulator of Phytoceramide Levels.
Cell Rep, 6:388-399, 2014

PubMed 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.

PubMed: 24412362
DOI: 10.1016/j.celrep.2013.12.023

Experimental method

X-RAY DIFFRACTION (2.403 Å)