| 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]
Publication Abstract from PubMed
Apicomplexan parasites such as Toxoplasma gondii and Plasmodium species actively invade host cells through a moving junction (MJ) complex assembled at the parasite-host cell interface. MJ assembly is initiated by injection of parasite rhoptry neck proteins (RONs) into the host cell, where RON2 spans the membrane and functions as a receptor for apical membrane antigen 1 (AMA1) on the parasite. We have determined the structure of TgAMA1 complexed with a RON2 peptide at 1.95 angstrom resolution. A stepwise assembly mechanism results in an extensive buried surface area, enabling the MJ complex to resist the mechanical forces encountered during host cell invasion. Besides providing insights into host cell invasion by apicomplexan parasites, the structure offers a basis for designing therapeutics targeting these global pathogens.
Host cell invasion by apicomplexan parasites: insights from the co-structure of AMA1 with a RON2 peptide.,Tonkin ML, Roques M, Lamarque MH, Pugniere M, Douguet D, Crawford J, Lebrun M, Boulanger MJ Science. 2011 Jul 22;333(6041):463-7. PMID:21778402[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:https://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:https://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:https://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:https://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:https://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:https://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:https://dx.doi.org/10.1073/pnas.1114661109
- ↑ Tonkin ML, Roques M, Lamarque MH, Pugniere M, Douguet D, Crawford J, Lebrun M, Boulanger MJ. Host cell invasion by apicomplexan parasites: insights from the co-structure of AMA1 with a RON2 peptide. Science. 2011 Jul 22;333(6041):463-7. PMID:21778402 doi:10.1126/science.1204988
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