Dephospho-CoA kinase, a nuclear-encoded apicoplast protein, remains active and essential after Plasmodium falciparum apicoplast disruption.
Plasmodium falciparum
DPCK
apicoplast
coenzyme A
malaria
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
16 08 2021
16 08 2021
Historique:
revised:
06
04
2021
received:
06
11
2020
accepted:
26
04
2021
pubmed:
26
5
2021
medline:
19
11
2021
entrez:
25
5
2021
Statut:
ppublish
Résumé
Malaria parasites contain an essential organelle called the apicoplast that houses metabolic pathways for fatty acid, heme, isoprenoid, and iron-sulfur cluster synthesis. Surprisingly, malaria parasites can survive without the apicoplast as long as the isoprenoid precursor isopentenyl pyrophosphate (IPP) is supplemented in the growth medium, making it appear that isoprenoid synthesis is the only essential function of the organelle in blood-stage parasites. In the work described here, we localized an enzyme responsible for coenzyme A synthesis, DPCK, to the apicoplast, but we were unable to delete DPCK, even in the presence of IPP. However, once the endogenous DPCK was complemented with the E. coli DPCK (EcDPCK), we were successful in deleting it. We were then able to show that DPCK activity is required for parasite survival through knockdown of the complemented EcDPCK. Additionally, we showed that DPCK enzyme activity remains functional and essential within the vesicles present after apicoplast disruption. These results demonstrate that while the apicoplast of blood-stage P. falciparum parasites can be disrupted, the resulting vesicles remain biochemically active and are capable of fulfilling essential functions.
Identifiants
pubmed: 34031901
doi: 10.15252/embj.2020107247
pmc: PMC8365264
doi:
Substances chimiques
Protozoan Proteins
0
Pantothenic Acid
19F5HK2737
Phosphotransferases (Alcohol Group Acceptor)
EC 2.7.1.-
dephospho-CoA kinase
EC 2.7.1.24
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e107247Subventions
Organisme : NIAID NIH HHS
ID : R01 AI065853
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI125534
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI101589
Pays : United States
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
Références
Mol Microbiol. 2010 Feb;75(4):957-71
pubmed: 20487290
Traffic. 2019 Aug;20(8):571-582
pubmed: 31094037
Cell Host Microbe. 2008 Dec 11;4(6):509-11
pubmed: 19064250
J Bacteriol. 2001 May;183(9):2774-8
pubmed: 11292795
Mol Biochem Parasitol. 2010 Aug;172(2):156-60
pubmed: 20403390
Cell Rep. 2017 Nov 14;21(7):1746-1756
pubmed: 29141210
mSphere. 2020 Aug 12;5(4):
pubmed: 32817449
PLoS Pathog. 2018 Apr 3;14(4):e1006918
pubmed: 29614109
Science. 2018 May 4;360(6388):
pubmed: 29724925
EMBO J. 2021 Aug 16;40(16):e107247
pubmed: 34031901
Antimicrob Agents Chemother. 2005 Feb;49(2):632-7
pubmed: 15673744
Cell Host Microbe. 2008 Dec 11;4(6):567-78
pubmed: 19064257
PLoS Pathog. 2011 Feb;7(2):e1001286
pubmed: 21379336
Sci Rep. 2014 Jul 11;4:5665
pubmed: 25012929
Proteins. 2010 Feb 15;78(3):575-88
pubmed: 19768685
Nat Commun. 2016 Jan 22;7:10519
pubmed: 26796412
Malar J. 2014 Aug 31;13:343
pubmed: 25174342
Nat Methods. 2006 Aug;3(8):615-21
pubmed: 16862136
Infect Disord Drug Targets. 2010 Jun;10(3):200-16
pubmed: 20334619
Antimicrob Agents Chemother. 2014;58(2):811-9
pubmed: 24247137
Nat Commun. 2014 Nov 05;5:5329
pubmed: 25370483
PLoS Pathog. 2016 Dec 27;12(12):e1006094
pubmed: 28027318
Mol Biochem Parasitol. 2002 Aug 28;123(2):85-94
pubmed: 12270624
Nat Biotechnol. 2014 Aug;32(8):819-21
pubmed: 24880488
Mol Microbiol. 2005 Jan;55(1):39-53
pubmed: 15612915
Antimicrob Agents Chemother. 2005 Nov;49(11):4649-57
pubmed: 16251308
J Biol Chem. 2009 Sep 11;284(37):24904-13
pubmed: 19584050
Proc Natl Acad Sci U S A. 2018 Mar 13;115(11):E2604-E2613
pubmed: 29483266
PLoS Pathog. 2020 Feb 14;16(2):e1008316
pubmed: 32059044
J Protozool. 1985 Nov;32(4):608-13
pubmed: 2866244
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7289-94
pubmed: 8692985
Front Cell Infect Microbiol. 2017 Jun 20;7:260
pubmed: 28676844
PLoS Biol. 2011 Aug;9(8):e1001138
pubmed: 21912516
PLoS Pathog. 2013;9(9):e1003655
pubmed: 24086138
EMBO J. 2000 Apr 17;19(8):1794-802
pubmed: 10775264
J Biol Chem. 2013 Jul 12;288(28):20558-67
pubmed: 23729665
Biochemistry. 2003 Feb 4;42(4):1160-9
pubmed: 12549938
Traffic. 2011 Sep;12(9):1124-38
pubmed: 21668595
Sci Transl Med. 2019 Sep 18;11(510):
pubmed: 31534021
Acta Crystallogr D Biol Crystallogr. 2003 Jul;59(Pt 7):1246-8
pubmed: 12832774
Mol Biochem Parasitol. 2015 Jan-Feb;199(1-2):34-50
pubmed: 25841762
Sci Rep. 2016 Jun 09;6:27531
pubmed: 27277538
Parasit Vectors. 2016 Nov 17;9(1):589
pubmed: 27855724
Nat Rev Microbiol. 2004 Mar;2(3):203-16
pubmed: 15083156
Cell Microbiol. 2009 Mar;11(3):506-20
pubmed: 19068099
FEMS Microbiol Rev. 2008 Jan;32(1):56-106
pubmed: 18173393
Nucleic Acids Res. 2015 Jan;43(Database issue):D1176-82
pubmed: 25593348
Eukaryot Cell. 2014 Nov;13(11):1348-59
pubmed: 25217461
Sci Rep. 2018 Oct 8;8(1):14902
pubmed: 30297725
PLoS One. 2013;8(2):e54974
pubmed: 23405100
Elife. 2020 Aug 20;9:
pubmed: 32815516
Antimicrob Agents Chemother. 2015;59(6):3666-8
pubmed: 25845876
Sci Rep. 2016 Sep 20;6:33518
pubmed: 27644319
J Biol Chem. 2001 May 25;276(21):18115-21
pubmed: 11278793
Antimicrob Agents Chemother. 2017 Dec 21;62(1):
pubmed: 29109165
PLoS Pathog. 2016 Jul 18;12(7):e1005734
pubmed: 27427910
Eukaryot Cell. 2014 May;13(5):550-9
pubmed: 24297444
Malar J. 2008 May 20;7:86
pubmed: 18492282