Abstract
Apicomplexan parasites such as Toxoplasma gondii contain a primitive plastid, the apicoplast, whose genome consists of a 35-kb circular DNA related to the plastid DNA of plants. Plants synthesize fatty acids in their plastids. The first committed step in fatty acid synthesis is catalyzed by acetyl-CoA carboxylase (ACC). This enzyme is encoded in the nucleus, synthesized in the cytosol, and transported into the plastid. In the present work, two genes encoding ACC from T. gondii were cloned and the gene structure was determined. Both ORFs encode multidomain proteins, each with an N-terminal extension, compared with the cytosolic ACCs from plants. The N-terminal extension of one isozyme, ACC1, was shown to target green fluorescent protein to the apicoplast of T. gondii . In addition, the apicoplast contains a biotinylated protein, consistent with the assertion that ACC1 is localized there. The second ACC in T. gondii appears to be cytosolic. T. gondii mitochondria also contain a biotinylated protein, probably pyruvate carboxylase. These results confirm the essential nature of the apicoplast and explain the inhibition of parasite growth in cultured cells by herbicides targeting ACC.
References
38
Referenced
98
-
D S Roos, M J Crawford, R G K Donald, J C Kissinger, L J Klimczak, B Striepen Curr Opin Microbiol 2, 426–432 (1999).
(
10.1016/S1369-5274(99)80075-7
) / Curr Opin Microbiol by Roos D S (1999) - R J M Wilson, D H Williamson Microbiol Mol Biol Rev 61, 1–16 (1997). / Microbiol Mol Biol Rev by Wilson R J M (1997)
-
G I McFadden, D S Roos Trends Microbiol 7, 328–333 (1999).
(
10.1016/S0966-842X(99)01547-4
) / Trends Microbiol by McFadden G I (1999) -
K M Hager, B Stripen, L G Tilney, D S Roos J Cell Sci 112, 2631–2638 (1999).
(
10.1242/jcs.112.16.2631
) / J Cell Sci by Hager K M (1999) -
R F Waller, P J Keeling, R G K Donald, B Striepen, E Handman, N Lang-Unnasch, A F Cowman, G S Besra, D S Roos, G I McFadden Proc Natl Acad Sci USA 95, 12352–12357 (1998).
(
10.1073/pnas.95.21.12352
) / Proc Natl Acad Sci USA by Waller R F (1998) -
R F Waller, M B Reed, A F Cowman, G I McFadden EMBO J 19, 1794–1802 (2000).
(
10.1093/emboj/19.8.1794
) / EMBO J by Waller R F (2000) -
M Lang, K E Apt, P G Kroth J Biol Chem 273, 30973–30978 (1998).
(
10.1074/jbc.273.47.30973
) / J Biol Chem by Lang M (1998) -
S D Schwartzbach, T Osafune, W Löffelhardt Plant Mol Biol 38, 247–263 (1998).
(
10.1023/A:1006029919283
) / Plant Mol Biol by Schwartzbach S D (1998) -
C Sulli, Z-W Fang, U Muchhal, S D Schwartzbach J Biol Chem 274, 457–463 (1999).
(
10.1074/jbc.274.1.457
) / J Biol Chem by Sulli C (1999) -
K Keegstra, K Cline Plant Cell 11, 557–570 (1999).
(
10.1105/tpc.11.4.557
) / Plant Cell by Keegstra K (1999) -
E Zuther, J J Johnson, R Haselkorn, R McLeod, P Gornicki Proc Natl Acad Sci USA 96, 13387–13392 (1999).
(
10.1073/pnas.96.23.13387
) / Proc Natl Acad Sci USA by Zuther E (1999) -
D S Roos, R G Donald, N S Morrissette, A L Moulton Methods Cell Biol 45, 27–63 (1994).
(
10.1016/S0091-679X(08)61845-2
) / Methods Cell Biol by Roos D S (1994) -
B Striepen, C Y X He, M Matrajt, D Soldati, D S Roos Mol Biochem Parasitol 92, 325–338 (1998).
(
10.1016/S0166-6851(98)00011-5
) / Mol Biochem Parasitol by Striepen B (1998) -
B Striepen, M J Crawford, M K Shaw, L G Tilney, F Seeber, D S Roos J Cell Biol 151, 1423–1433 (2000).
(
10.1083/jcb.151.7.1423
) / J Cell Biol by Striepen B (2000) -
P Gornicki, J Faris, I King, J Podkowinski, B Gill, R Haselkorn Proc Natl Acad Sci USA 94, 14179–14185 (1997).
(
10.1073/pnas.94.25.14179
) / Proc Natl Acad Sci USA by Gornicki P (1997) -
J Podkowinski, G E Sroga, R Haselkorn, P Gornicki Proc Natl Acad Sci USA 93, 1870–1874 (1996).
(
10.1073/pnas.93.5.1870
) / Proc Natl Acad Sci USA by Podkowinski J (1996) -
S Jitrapakdee, J C Wallace Biochem J 340, 1–16 (1999).
(
10.1042/bj3400001
) / Biochem J by Jitrapakdee S (1999) -
P Gornicki, J Podkowinski, L A Scappino, J DiMaio, E Ward, R Haselkorn Proc Natl Acad Sci USA 91, 6860–6864 (1994).
(
10.1073/pnas.91.15.6860
) / Proc Natl Acad Sci USA by Gornicki P (1994) -
W Schulte, R Topfer, R Stracke, J Schell, N Martini Proc Natl Acad Sci USA 94, 3465–3470 (1997).
(
10.1073/pnas.94.7.3465
) / Proc Natl Acad Sci USA by Schulte W (1997) -
P G Roessler, J B Ohlrogge J Biol Chem 268, 19254–19259 (1993).
(
10.1016/S0021-9258(19)36507-X
) / J Biol Chem by Roessler P G (1993) - J T Christopher, J A M Holtum Aust J Plant Phys 27, 845–850 (2000). / Aust J Plant Phys by Christopher J T (2000)
-
A Golz, M Focke, H K Lichtenthaler J Plant Physiol 143, 426–433 (1994).
(
10.1016/S0176-1617(11)81802-X
) / J Plant Physiol by Golz A (1994) -
T Konishi, Y Sasaki Proc Natl Acad Sci USA 91, 3598–3601 (1994).
(
10.1073/pnas.91.9.3598
) / Proc Natl Acad Sci USA by Konishi T (1994) -
T Nikolskaya, O Zagnitko, G Tevzadze, R Haselkorn, P Gornicki Proc Natl Acad Sci USA 96, 14647–14651 (1999).
(
10.1073/pnas.96.25.14647
) / Proc Natl Acad Sci USA by Nikolskaya T (1999) -
W Martin, B Stoebe, V Goremykin, S Hansmann, M Hasegava, K V Kowallik Nature (London) 393, 162–165 (1998).
(
10.1038/30234
) / Nature (London) by Martin W (1998) - J B Ohlrogge, J G Jaworski, D Post-Beittenmiller Lipid Metabolism in Plants (CRC, Boca Raton, FL), pp. 3–32 (1993). / Lipid Metabolism in Plants by Ohlrogge J B (1993)
-
J Ke, R H Behal, S L Back, B J Nikolau, E S Wurtele, D J Oliver Plant Physiol 123, 497–508 (2000).
(
10.1104/pp.123.2.497
) / Plant Physiol by Ke J (2000) -
D Post-Beittenmiller Annu Rev Plant Physiol Plant Mol Biol 47, 405–430 (1996).
(
10.1146/annurev.arplant.47.1.405
) / Annu Rev Plant Physiol Plant Mol Biol by Post-Beittenmiller D (1996) -
V Gueguen, D Macherel, M Jaquinod, R Douce, J Bourguignon J Biol Chem 275, 5016–5025 (2000).
(
10.1074/jbc.275.7.5016
) / J Biol Chem by Gueguen V (2000) -
C J M Beckers, D S Roos, R G K Donald, B J Luft, J C Schwab, Y Cao, K A Joiner J Clin Invest 95, 367–376 (1995).
(
10.1172/JCI117665
) / J Clin Invest by Beckers C J M (1995) -
M E Fichera, M K Bhopale, D S Roos Antimicrob Agents Chemother 39, 1530–1537 (1995).
(
10.1128/AAC.39.7.1530
) / Antimicrob Agents Chemother by Fichera M E (1995) -
E R Pfefferkorn, R F Nothnagel, S E Borotz Antimicrob Agents Chemother 36, 1091–1096 (1992).
(
10.1128/AAC.36.5.1091
) / Antimicrob Agents Chemother by Pfefferkorn E R (1992) -
M E Fichera, D S Roos Nature (London) 390, 407–409 (1997).
(
10.1038/37132
) / Nature (London) by Fichera M E (1997) -
H Jomaa, J Wiesner, S Sanderbrand, B Altincicek, C Weidemeyer, M Hintz, I Turbachova, M Ebert, J Zeidler, H K Lichtenthaler, et al. Science 285, 1573–1576 (1999).
(
10.1126/science.285.5433.1573
) / Science by Jomaa H (1999) -
J W Ajioka, J C Boothroyd, B P Brunk, A Hehl, L Hiller, I D Manger, M Marra, G C Overton, D S Roos, K-L Wan, et al. Genome Res 8, 18–28 (1998).
(
10.1101/gr.8.1.18
) / Genome Res by Ajioka J W (1998) -
S Bowman, D Lawson, D Basham, D Brown, T Chillingworth, C M Churcher, A Craig, R M Davies, K Devlin, T Feltwell, et al. Nature (London) 400, 532–538 (1999).
(
10.1038/22964
) / Nature (London) by Bowman S (1999) -
M J Gardner, H Tettelin, D J Carucci, L M Cummings, L Aravind, E V Koonin, S Shallom, T Mason, K Yu, C Fujii, et al. Science 282, 1126–1132 (1998).
(
10.1126/science.282.5391.1126
) / Science by Gardner M J (1998) -
R Schneiter, M Hitomi, A S Ivessa, E-V Fasch, S D Kohlwein, A M Tartakoff Mol Cell Biol 16, 7161–7172 (1996).
(
10.1128/MCB.16.12.7161
) / Mol Cell Biol by Schneiter R (1996)
Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 10:45 a.m.) |
Deposited | 3 years, 2 months ago (June 7, 2022, 1:28 a.m.) |
Indexed | 1 month, 2 weeks ago (July 14, 2025, 11:36 p.m.) |
Issued | 24 years, 6 months ago (Feb. 13, 2001) |
Published | 24 years, 6 months ago (Feb. 13, 2001) |
Published Online | 24 years, 6 months ago (Feb. 13, 2001) |
Published Print | 24 years, 6 months ago (Feb. 27, 2001) |
@article{Jelenska_2001, title={Subcellular localization of acetyl-CoA carboxylase in the apicomplexan parasite Toxoplasma gondii}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.051629998}, DOI={10.1073/pnas.051629998}, number={5}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Jelenska, J. and Crawford, M. J. and Harb, O. S. and Zuther, E. and Haselkorn, R. and Roos, D. S. and Gornicki, P.}, year={2001}, month=feb, pages={2723–2728} }