| Structural highlights
Function
[PLDA1_ARATH] Hydrolyzes glycerol-phospholipids at the terminal phosphodiesteric bond to generate phosphatidic acids (PA). Plays an important role in various cellular processes, including phytohormone action and response to stress, characterized by acidification of the cell (PubMed:9437863). Involved in wound induction of jasmonic acid (PubMed:11090221). May be involved in membrane lipid remodeling (PubMed:11239826). Probably involved in freezing tolerance by modulating the cold-responsive genes and accumulation of osmolytes (PubMed:16949955). Can use phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) as substrates, both in presence or in absence of PIP2 (PubMed:9578608). Its main substrate is phosphatidylcholine (PubMed:11239826). Stimulates the intrinsic GTPase activity of GPA1 upon binding (PubMed:14594812). Mediates the abscisic acid effects on stomata through interaction with GPA1 and the production of phosphatidic acid that bind to ABI1 (PubMed:17261695, PubMed:17565616). Involved in seed aging and deterioration (PubMed:17565616). Involved in microtubule stabilization and salt tolerance (PubMed:23150630). Involved in abscisic acid-induced stomatal closure (PubMed:22392280).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]
Publication Abstract from PubMed
Phospholipase D (PLD) hydrolyzes the phosphodiester bond of glycerophospholipids and produces phosphatidic acid (PA), which acts as a second messenger in many living organisms. A large number of PLDs have been identified in eukaryotes, and are viewed as promising targets for drug design because these enzymes are known to be tightly regulated and to function in the pathophysiology of many human diseases. However, the underlying molecular mechanisms of catalysis and regulation of eukaryotic PLD remain elusive. Here, we determined the crystal structure of full-length plant PLDalpha1 in the apo state and in complex with PA. The structure shows that the N-terminal C2 domain hydrophobically interacts with the C-terminal catalytic domain that features two HKD motifs. Our analysis reveals the catalytic site, substrate-binding mechanism, and a new Ca(2+)-binding site that is required for the activation of PLD. In addition, we tested several efficient small-molecule inhibitors against PLDalpha1, and suggested a possible competitive inhibition mechanism according to structure-based docking analysis. This study explains many long-standing questions about PLDs and provides structural insights into PLD-targeted inhibitor/drug design.
Crystal structure of plant PLDalpha1 reveals catalytic and regulatory mechanisms of eukaryotic phospholipase D.,Li J, Yu F, Guo H, Xiong R, Zhang W, He F, Zhang M, Zhang P Cell Res. 2019 Oct 16. pii: 10.1038/s41422-019-0244-6. doi:, 10.1038/s41422-019-0244-6. PMID:31619765[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pappan K, Wang X. Plant phospholipase Dalpha is an acidic phospholipase active at near-physiological Ca(2+) concentrations. Arch Biochem Biophys. 1999 Aug 15;368(2):347-53. doi: 10.1006/abbi.1999.1325. PMID:10441386 doi:https://dx.doi.org/10.1006/abbi.1999.1325
- ↑ Wang C, Zien CA, Afitlhile M, Welti R, Hildebrand DF, Wang X. Involvement of phospholipase D in wound-induced accumulation of jasmonic acid in arabidopsis. Plant Cell. 2000 Nov;12(11):2237-46. doi: 10.1105/tpc.12.11.2237. PMID:11090221 doi:https://dx.doi.org/10.1105/tpc.12.11.2237
- ↑ Zien CA, Wang C, Wang X, Welti R. In vivo substrates and the contribution of the common phospholipase D, PLDalpha, to wound-induced metabolism of lipids in Arabidopsis. Biochim Biophys Acta. 2001 Feb 26;1530(2-3):236-48. doi:, 10.1016/s1388-1981(01)00091-9. PMID:11239826 doi:https://dx.doi.org/10.1016/s1388-1981(01)00091-9
- ↑ Zhao J, Wang X. Arabidopsis phospholipase Dalpha1 interacts with the heterotrimeric G-protein alpha-subunit through a motif analogous to the DRY motif in G-protein-coupled receptors. J Biol Chem. 2004 Jan 16;279(3):1794-800. doi: 10.1074/jbc.M309529200. Epub 2003 , Oct 31. PMID:14594812 doi:https://dx.doi.org/10.1074/jbc.M309529200
- ↑ Mishra G, Zhang W, Deng F, Zhao J, Wang X. A bifurcating pathway directs abscisic acid effects on stomatal closure and opening in Arabidopsis. Science. 2006 Apr 14;312(5771):264-6. PMID:16614222 doi:312/5771/264
- ↑ Rajashekar CB, Zhou HE, Zhang Y, Li W, Wang X. Suppression of phospholipase Dalpha1 induces freezing tolerance in Arabidopsis: response of cold-responsive genes and osmolyte accumulation. J Plant Physiol. 2006 Sep;163(9):916-26. doi: 10.1016/j.jplph.2005.08.006. Epub, 2005 Oct 5. PMID:16949955 doi:https://dx.doi.org/10.1016/j.jplph.2005.08.006
- ↑ Mane SP, Vasquez-Robinet C, Sioson AA, Heath LS, Grene R. Early PLDalpha-mediated events in response to progressive drought stress in Arabidopsis: a transcriptome analysis. J Exp Bot. 2007;58(2):241-52. doi: 10.1093/jxb/erl262. PMID:17261695 doi:https://dx.doi.org/10.1093/jxb/erl262
- ↑ Devaiah SP, Pan X, Hong Y, Roth M, Welti R, Wang X. Enhancing seed quality and viability by suppressing phospholipase D in Arabidopsis. Plant J. 2007 Jun;50(6):950-7. doi: 10.1111/j.1365-313X.2007.03103.x. PMID:17565616 doi:https://dx.doi.org/10.1111/j.1365-313X.2007.03103.x
- ↑ Uraji M, Katagiri T, Okuma E, Ye W, Hossain MA, Masuda C, Miura A, Nakamura Y, Mori IC, Shinozaki K, Murata Y. Cooperative function of PLDdelta and PLDalpha1 in abscisic acid-induced stomatal closure in Arabidopsis. Plant Physiol. 2012 May;159(1):450-60. doi: 10.1104/pp.112.195578. Epub 2012 Mar , 5. PMID:22392280 doi:https://dx.doi.org/10.1104/pp.112.195578
- ↑ Zhang Q, Lin F, Mao T, Nie J, Yan M, Yuan M, Zhang W. Phosphatidic acid regulates microtubule organization by interacting with MAP65-1 in response to salt stress in Arabidopsis. Plant Cell. 2012 Nov;24(11):4555-76. doi: 10.1105/tpc.112.104182. Epub 2012 Nov, 13. PMID:23150630 doi:https://dx.doi.org/10.1105/tpc.112.104182
- ↑ Fan L, Zheng S, Wang X. Antisense suppression of phospholipase D alpha retards abscisic acid- and ethylene-promoted senescence of postharvest Arabidopsis leaves. Plant Cell. 1997 Dec;9(12):2183-96. doi: 10.1105/tpc.9.12.2183. PMID:9437863 doi:https://dx.doi.org/10.1105/tpc.9.12.2183
- ↑ Pappan K, Austin-Brown S, Chapman KD, Wang X. Substrate selectivities and lipid modulation of plant phospholipase D alpha, -beta, and -gamma. Arch Biochem Biophys. 1998 May 1;353(1):131-40. doi: 10.1006/abbi.1998.0640. PMID:9578608 doi:https://dx.doi.org/10.1006/abbi.1998.0640
- ↑ Li J, Yu F, Guo H, Xiong R, Zhang W, He F, Zhang M, Zhang P. Crystal structure of plant PLDalpha1 reveals catalytic and regulatory mechanisms of eukaryotic phospholipase D. Cell Res. 2019 Oct 16. pii: 10.1038/s41422-019-0244-6. doi:, 10.1038/s41422-019-0244-6. PMID:31619765 doi:https://dx.doi.org/10.1038/s41422-019-0244-6
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