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| | ==MIC5 regulates the activity of Toxoplasma subtilisin 1 by mimicking a subtilisin prodomain== | | ==MIC5 regulates the activity of Toxoplasma subtilisin 1 by mimicking a subtilisin prodomain== |
| - | <StructureSection load='2lu2' size='340' side='right' caption='[[2lu2]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2lu2' size='340' side='right'caption='[[2lu2]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2lu2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Toxgo Toxgo]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LU2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LU2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2lu2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LU2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LU2 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TGME49_077080, TGVEG_027740 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5811 TOXGO])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2lu2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lu2 OCA], [http://pdbe.org/2lu2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lu2 RCSB], [http://www.ebi.ac.uk/pdbsum/2lu2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2lu2 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2lu2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lu2 OCA], [https://pdbe.org/2lu2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lu2 RCSB], [https://www.ebi.ac.uk/pdbsum/2lu2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lu2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Toxgo]] | + | [[Category: Large Structures]] |
| - | [[Category: Carruthers, V B]] | + | [[Category: Toxoplasma gondii]] |
| - | [[Category: Dou, Z]] | + | [[Category: Carruthers VB]] |
| - | [[Category: Henry, M]] | + | [[Category: Dou Z]] |
| - | [[Category: Marchant, J]] | + | [[Category: Henry M]] |
| - | [[Category: Matthews, S]] | + | [[Category: Marchant J]] |
| - | [[Category: Saouros, S]] | + | [[Category: Matthews S]] |
| - | [[Category: Cell adhesion]]
| + | [[Category: Saouros S]] |
| - | [[Category: Invasion]]
| + | |
| - | [[Category: Micronemal protein 5]]
| + | |
| - | [[Category: Pathogenesis]]
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| Structural highlights
Publication Abstract from PubMed
Toxoplasma gondii is the model parasite of the phylum Apicomplexa, which contains obligate intracellular parasites of medical and veterinary importance. Apicomplexans invade host cells by a multistep process involving the secretion of adhesive microneme protein (MIC) complexes. The subtilisin protease TgSUB1 trims several MICs on the parasite surface to activate gliding motility and host invasion. Although a previous study showed that expression of the secretory protein TgMIC5 suppresses TgSUB1 activity, the mechanism was unknown. Here, we solve the three-dimensional structure of TgMIC5 by nuclear magnetic resonance (NMR), revealing that it mimics a subtilisin prodomain including a flexible C-terminal peptide that may insert into the subtilisin active site. We show that TgMIC5 is an almost 50-fold more potent inhibitor of TgSUB1 activity than the small molecule inhibitor N-[N-(N-acetyl-l-leucyl)-l-leucyl]-l-norleucine (ALLN). Moreover, we demonstrate that TgMIC5 is retained on the parasite plasma membrane via its physical interaction with the membrane-anchored TgSUB1.
Microneme protein 5 regulates the activity of toxoplasma subtilisin 1 by mimicking a subtilisin prodomain.,Saouros S, Dou Z, Henry M, Marchant J, Carruthers VB, Matthews S J Biol Chem. 2012 Oct 19;287(43):36029-40. doi: 10.1074/jbc.M112.389825. Epub, 2012 Aug 15. PMID:22896704[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Saouros S, Dou Z, Henry M, Marchant J, Carruthers VB, Matthews S. Microneme protein 5 regulates the activity of toxoplasma subtilisin 1 by mimicking a subtilisin prodomain. J Biol Chem. 2012 Oct 19;287(43):36029-40. doi: 10.1074/jbc.M112.389825. Epub, 2012 Aug 15. PMID:22896704 doi:http://dx.doi.org/10.1074/jbc.M112.389825
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