Proteopedia

4ntg

Crystal structure of D60A mutant of Arabidopsis ACD11 (accelerated-cell-death 11) complexed with C12 ceramide-1-phosphate (d18:1/12:0) at 2.55 Angstrom resolutionCrystal structure of D60A mutant of Arabidopsis ACD11 (accelerated-cell-death 11) complexed with C12 ceramide-1-phosphate (d18:1/12:0) at 2.55 Angstrom resolution

Structural highlights

4ntg is a 2 chain structure with sequence from Arabidopsis thaliana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5505Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ACD11_ARATH Exhibits selective intermembrane transfer of ceramide-1-phosphate (C1P) and phytoceramide-1-phosphate (PubMed:24412362, PubMed:28011644). Does not transport ceramide (Cer) or GalCer, suggesting a requirement for phosphate in the headgroup for functionality (PubMed:24412362). Transports in vitro sphingosine, but not glycosphingolipids (PubMed:11850411). Has also some in vitro activity with sphingomyelin, a lipid not detected in plant tissues (PubMed:18657186). The transport function may be not directly involved in regulating cell death. Rather, perturbations in the function of ACD11 or related components could be monitored by R-proteins, which then mediate defense and programmed cell death (PCD), as proposed in the guard hypothesis (Probable). C1P transfer is stimulated by phosphatidylserine in C1P source vesicles (PubMed:28011644). Regulates autophagy, inflammasome mediated IL1B and IL18 processing, and pyroptosis, but not apoptosis (PubMed:28011644).[1] [2] [3] [4] [5]

Publication Abstract from PubMed

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 pi helix (pi bulge) near the lipid binding cleft distinguishes apo-ACD11 from other GLTP folds. The global two-layer, alpha-helically dominated, "sandwich" topology displaying C1P-selective binding identifies ACD11 as the plant prototype of a GLTP fold subfamily.

Arabidopsis Accelerated Cell Death 11, ACD11, Is a Ceramide-1-Phosphate Transfer Protein and Intermediary Regulator of Phytoceramide Levels.,Simanshu DK, Zhai X, Munch D, Hofius D, Markham JE, Bielawski J, Bielawska A, Malinina L, Molotkovsky JG, Mundy JW, Patel DJ, Brown RE Cell Rep. 2014 Jan 30;6(2):388-99. doi: 10.1016/j.celrep.2013.12.023. Epub 2014, Jan 9. PMID:24412362[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Brodersen P, Petersen M, Pike HM, Olszak B, Skov S, Odum N, Jorgensen LB, Brown RE, Mundy J. Knockout of Arabidopsis accelerated-cell-death11 encoding a sphingosine transfer protein causes activation of programmed cell death and defense. Genes Dev. 2002 Feb 15;16(4):490-502. doi: 10.1101/gad.218202. PMID:11850411 doi:http://dx.doi.org/10.1101/gad.218202
  2. ↑ Petersen NH, McKinney LV, Pike H, Hofius D, Zakaria A, Brodersen P, Petersen M, Brown RE, Mundy J. Human GLTP and mutant forms of ACD11 suppress cell death in the Arabidopsis acd11 mutant. FEBS J. 2008 Sep;275(17):4378-88. doi: 10.1111/j.1742-4658.2008.06584.x. Epub , 2008 Jul 24. PMID:18657186 doi:http://dx.doi.org/10.1111/j.1742-4658.2008.06584.x
  3. ↑ Simanshu DK, Zhai X, Munch D, Hofius D, Markham JE, Bielawski J, Bielawska A, Malinina L, Molotkovsky JG, Mundy JW, Patel DJ, Brown RE. Arabidopsis Accelerated Cell Death 11, ACD11, Is a Ceramide-1-Phosphate Transfer Protein and Intermediary Regulator of Phytoceramide Levels. Cell Rep. 2014 Jan 30;6(2):388-99. doi: 10.1016/j.celrep.2013.12.023. Epub 2014, Jan 9. PMID:24412362 doi:http://dx.doi.org/10.1016/j.celrep.2013.12.023
  4. ↑ Zhai X, Gao YG, Mishra SK, Simanshu DK, Boldyrev IA, Benson LM, Bergen HR 3rd, Malinina L, Mundy J, Molotkovsky JG, Patel DJ, Brown RE. Phosphatidylserine Stimulates Ceramide 1-Phosphate (C1P) Intermembrane Transfer by C1P Transfer Proteins. J Biol Chem. 2017 Feb 10;292(6):2531-2541. doi: 10.1074/jbc.M116.760256. Epub , 2016 Dec 23. PMID:28011644 doi:http://dx.doi.org/10.1074/jbc.M116.760256
  5. ↑ Petersen NH, Joensen J, McKinney LV, Brodersen P, Petersen M, Hofius D, Mundy J. Identification of proteins interacting with Arabidopsis ACD11. J Plant Physiol. 2009 Apr 1;166(6):661-6. doi: 10.1016/j.jplph.2008.08.003. Epub , 2008 Oct 8. PMID:18845362 doi:http://dx.doi.org/10.1016/j.jplph.2008.08.003
  6. ↑ Simanshu DK, Zhai X, Munch D, Hofius D, Markham JE, Bielawski J, Bielawska A, Malinina L, Molotkovsky JG, Mundy JW, Patel DJ, Brown RE. Arabidopsis Accelerated Cell Death 11, ACD11, Is a Ceramide-1-Phosphate Transfer Protein and Intermediary Regulator of Phytoceramide Levels. Cell Rep. 2014 Jan 30;6(2):388-99. doi: 10.1016/j.celrep.2013.12.023. Epub 2014, Jan 9. PMID:24412362 doi:http://dx.doi.org/10.1016/j.celrep.2013.12.023

4ntg, resolution 2.55Å

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