| Structural highlights
Function
[AMA1_TOXGO] Essential microneme protein that plays an important role in host cell invasion. Part of the moving junction (MJ) complex, a ringlike structure formed between the plasma membranes of the apical tip of the parasite and the target host cell. During invasion, the MJ migrates from the anterior to the posterior of the parasite, leading to internalization of the parasite into a parasitophorous vacuole (PV).[1] [2] [3] [4] [5] [6] [7] [8] [9]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Apical membrane antigen 1 (AMA1) is an essential component of the moving junction complex used by Apicomplexan parasites to invade host cells. We report the 2.0 A resolution x-ray crystal structure of the full ectodomain (domains I, II, and III) of AMA1 from the pervasive protozoan parasite Toxoplasma gondii. The structure of T. gondii AMA1 (TgAMA1) is the most complete of any AMA1 structure to date, with more than 97.5% of the ectodomain unambiguously modeled. Comparative sequence analysis reveals discrete segments of divergence in TgAMA1 that map to areas of established functional importance in AMA1 from Plasmodium vivax (PvAMA1) and Plasmodium falciparum (PfAMA1). Inspection of the TgAMA1 structure reveals a network of apical surface loops, reorganized in both size and chemistry relative to PvAMA1/PfAMA1, that appear to serve as structural filters restricting access to a central hydrophobic groove. The terminal portion of this groove is formed by an extended loop from DII that is 14 residues shorter in TgAMA1. A pair of tryptophan residues (Trp(353) and Trp(354)) anchor the DII loop in the hydrophobic groove and frame a conserved tyrosine (Tyr(230)), forming a contiguous surface that may be critical for moving junction assembly. The minimalist DIII structure folds into a cystine knot that probably stabilizes and orients the bulk of the ectodmain without providing excess surface area to which invasion-inhibitory antibodies can be generated. The detailed structural characterization of TgAMA1 provides valuable insight into the mechanism of host cell invasion by T. gondii.
Structural characterization of apical membrane antigen 1 (AMA1) from Toxoplasma gondii.,Crawford J, Tonkin ML, Grujic O, Boulanger MJ J Biol Chem. 2010 May 14;285(20):15644-52. Epub 2010 Mar 19. PMID:20304917[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hehl AB, Lekutis C, Grigg ME, Bradley PJ, Dubremetz JF, Ortega-Barria E, Boothroyd JC. Toxoplasma gondii homologue of plasmodium apical membrane antigen 1 is involved in invasion of host cells. Infect Immun. 2000 Dec;68(12):7078-86. PMID:11083833
- ↑ Donahue CG, Carruthers VB, Gilk SD, Ward GE. The Toxoplasma homolog of Plasmodium apical membrane antigen-1 (AMA-1) is a microneme protein secreted in response to elevated intracellular calcium levels. Mol Biochem Parasitol. 2000 Nov;111(1):15-30. PMID:11087913
- ↑ Mital J, Meissner M, Soldati D, Ward GE. Conditional expression of Toxoplasma gondii apical membrane antigen-1 (TgAMA1) demonstrates that TgAMA1 plays a critical role in host cell invasion. Mol Biol Cell. 2005 Sep;16(9):4341-9. Epub 2005 Jul 6. PMID:16000372 doi:http://dx.doi.org/10.1091/mbc.E05-04-0281
- ↑ Howell SA, Hackett F, Jongco AM, Withers-Martinez C, Kim K, Carruthers VB, Blackman MJ. Distinct mechanisms govern proteolytic shedding of a key invasion protein in apicomplexan pathogens. Mol Microbiol. 2005 Sep;57(5):1342-56. PMID:16102004 doi:http://dx.doi.org/10.1111/j.1365-2958.2005.04772.x
- ↑ Alexander DL, Mital J, Ward GE, Bradley P, Boothroyd JC. Identification of the moving junction complex of Toxoplasma gondii: a collaboration between distinct secretory organelles. PLoS Pathog. 2005 Oct;1(2):e17. Epub 2005 Oct 21. PMID:16244709 doi:http://dx.doi.org/10.1371/journal.ppat.0010017
- ↑ Besteiro S, Michelin A, Poncet J, Dubremetz JF, Lebrun M. Export of a Toxoplasma gondii rhoptry neck protein complex at the host cell membrane to form the moving junction during invasion. PLoS Pathog. 2009 Feb;5(2):e1000309. doi: 10.1371/journal.ppat.1000309. Epub 2009, Feb 27. PMID:19247437 doi:http://dx.doi.org/10.1371/journal.ppat.1000309
- ↑ Buguliskis JS, Brossier F, Shuman J, Sibley LD. Rhomboid 4 (ROM4) affects the processing of surface adhesins and facilitates host cell invasion by Toxoplasma gondii. PLoS Pathog. 2010 Apr 22;6(4):e1000858. doi: 10.1371/journal.ppat.1000858. PMID:20421941 doi:http://dx.doi.org/10.1371/journal.ppat.1000858
- ↑ Santos JM, Ferguson DJ, Blackman MJ, Soldati-Favre D. Intramembrane cleavage of AMA1 triggers Toxoplasma to switch from an invasive to a replicative mode. Science. 2011 Jan 28;331(6016):473-7. doi: 10.1126/science.1199284. Epub 2010 Dec, 23. PMID:21205639 doi:http://dx.doi.org/10.1126/science.1199284
- ↑ Parussini F, Tang Q, Moin SM, Mital J, Urban S, Ward GE. Intramembrane proteolysis of Toxoplasma apical membrane antigen 1 facilitates host-cell invasion but is dispensable for replication. Proc Natl Acad Sci U S A. 2012 May 8;109(19):7463-8. doi:, 10.1073/pnas.1114661109. Epub 2012 Apr 20. PMID:22523242 doi:http://dx.doi.org/10.1073/pnas.1114661109
- ↑ Crawford J, Tonkin ML, Grujic O, Boulanger MJ. Structural characterization of apical membrane antigen 1 (AMA1) from Toxoplasma gondii. J Biol Chem. 2010 May 14;285(20):15644-52. Epub 2010 Mar 19. PMID:20304917 doi:10.1074/jbc.M109.092619
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