View source for 4nti


==Crystal structure of D60N mutant of Arabidopsis ACD11 (accelerated-cell-death 11) complexed with C12 ceramide-1-phosphate (d18:1/12:0) at 2.9 Angstrom resolution==
<StructureSection load='4nti' size='340' side='right'caption='[[4nti]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4nti]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NTI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.899&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PZ:(2S,3R,4E)-2-(DODECANOYLAMINO)-3-HYDROXYOCTADEC-4-EN-1-YL+DIHYDROGEN+PHOSPHATE'>1PZ</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4nti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nti OCA], [https://pdbe.org/4nti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nti RCSB], [https://www.ebi.ac.uk/pdbsum/4nti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nti ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ACD11_ARATH 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).<ref>PMID:11850411</ref> <ref>PMID:18657186</ref> <ref>PMID:24412362</ref> <ref>PMID:28011644</ref> <ref>PMID:18845362</ref> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:24412362</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4nti" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Arabidopsis thaliana]]
[[Category: Large Structures]]
[[Category: Brown RE]]
[[Category: Patel DJ]]
[[Category: Simanshu DK]]