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| | <StructureSection load='6d7a' size='340' side='right'caption='[[6d7a]], [[Resolution|resolution]] 1.13Å' scene=''> | | <StructureSection load='6d7a' size='340' side='right'caption='[[6d7a]], [[Resolution|resolution]] 1.13Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6d7a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Toxgo Toxgo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D7A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D7A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6d7a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D7A FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.13Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5811 TOXGO])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=6d7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d7a OCA], [http://pdbe.org/6d7a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d7a RCSB], [http://www.ebi.ac.uk/pdbsum/6d7a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d7a 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=6d7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d7a OCA], [https://pdbe.org/6d7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d7a RCSB], [https://www.ebi.ac.uk/pdbsum/6d7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d7a ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PLP1_TOXGV PLP1_TOXGV] Pore-forming protein that promotes parasite exit from host cells: mediates formation of a pore in the parasitophorous vacuolar membrane, leading to membrane permeabilization, thereby facilitating parasite egress from host cells (PubMed:19095897, PubMed:29750191, PubMed:30513119). May also form a pore in the host plasma membrane (PubMed:19095897). Preferentially binds inner leaflet lipids, such as phosphatidylethanolamine (PE) or phosphatidylserine (PS) (PubMed:30513119).<ref>PMID:19095897</ref> <ref>PMID:29750191</ref> <ref>PMID:30513119</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6d7a" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6d7a" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Cytolysin 3D structures|Cytolysin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Toxgo]] | + | [[Category: Toxoplasma gondii]] |
| - | [[Category: Bahr, C M.E]] | + | [[Category: Bahr CME]] |
| - | [[Category: Carruthers, V B]] | + | [[Category: Carruthers VB]] |
| - | [[Category: Guerra, A J]] | + | [[Category: Guerra AJ]] |
| - | [[Category: Koropatkin, N M]] | + | [[Category: Koropatkin NM]] |
| - | [[Category: Wawrzak, Z]] | + | [[Category: Wawrzak Z]] |
| - | [[Category: Beta-prism]]
| + | |
| - | [[Category: Lipid binding protein]]
| + | |
| - | [[Category: Perforin-like protein]]
| + | |
| - | [[Category: Pore forming protein]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
PLP1_TOXGV Pore-forming protein that promotes parasite exit from host cells: mediates formation of a pore in the parasitophorous vacuolar membrane, leading to membrane permeabilization, thereby facilitating parasite egress from host cells (PubMed:19095897, PubMed:29750191, PubMed:30513119). May also form a pore in the host plasma membrane (PubMed:19095897). Preferentially binds inner leaflet lipids, such as phosphatidylethanolamine (PE) or phosphatidylserine (PS) (PubMed:30513119).[1] [2] [3]
Publication Abstract from PubMed
Intracellular pathogens must egress from the host cell to continue their infectious cycle. Apicomplexans are a phylum of intracellular protozoans that have evolved members of the membrane attack complex and perforin (MACPF) family of pore forming proteins to disrupt cellular membranes for traversing cells during tissue migration or egress from a replicative vacuole following intracellular reproduction. Previous work showed that the apicomplexan Toxoplasma gondii secretes a perforin-like protein (TgPLP1) that contains a C-terminal Domain (CTD) which is necessary for efficient parasite egress. However, the structural basis for CTD membrane binding and egress competency remained unknown. Here, we present evidence that TgPLP1 CTD prefers binding lipids that are abundant in the inner leaflet of the lipid bilayer. Additionally, solving the high-resolution crystal structure of the TgPLP1 APCbeta domain within the CTD reveals an unusual double-layered beta-prism fold that resembles only one other protein of known structure. Three direct repeat sequences comprise subdomains, with each constituting a wall of the beta-prism fold. One subdomain features a protruding hydrophobic loop with an exposed tryptophan at its tip. Spectrophotometric measurements of intrinsic tryptophan fluorescence are consistent with insertion of the hydrophobic loop into a target membrane. Using CRISPR/Cas9 gene editing we show that parasite strains bearing mutations in the hydrophobic loop, including alanine substitution of the tip tryptophan, are equally deficient in egress as a strain lacking TgPLP1 altogether. Taken together our findings suggest a crucial role for the hydrophobic loop in anchoring TgPLP1 to the membrane to support its cytolytic activity and egress function.
Structural basis of Toxoplasma gondii perforin-like protein 1 membrane interaction and activity during egress.,Guerra AJ, Zhang O, Bahr CME, Huynh MH, DelProposto J, Brown WC, Wawrzak Z, Koropatkin NM, Carruthers VB PLoS Pathog. 2018 Dec 4;14(12):e1007476. doi: 10.1371/journal.ppat.1007476., eCollection 2018 Dec. PMID:30513119[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kafsack BF, Pena JD, Coppens I, Ravindran S, Boothroyd JC, Carruthers VB. Rapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells. Science. 2009 Jan 23;323(5913):530-3. PMID:19095897 doi:10.1126/science.1165740
- ↑ Ni T, Williams SI, Rezelj S, Anderluh G, Harlos K, Stansfeld PJ, Gilbert RJC. Structures of monomeric and oligomeric forms of the Toxoplasma gondii perforin-like protein 1. Sci Adv. 2018 Mar 21;4(3):eaaq0762. doi: 10.1126/sciadv.aaq0762. eCollection 2018, Mar. PMID:29750191 doi:http://dx.doi.org/10.1126/sciadv.aaq0762
- ↑ Guerra AJ, Zhang O, Bahr CME, Huynh MH, DelProposto J, Brown WC, Wawrzak Z, Koropatkin NM, Carruthers VB. Structural basis of Toxoplasma gondii perforin-like protein 1 membrane interaction and activity during egress. PLoS Pathog. 2018 Dec 4;14(12):e1007476. doi: 10.1371/journal.ppat.1007476., eCollection 2018 Dec. PMID:30513119 doi:http://dx.doi.org/10.1371/journal.ppat.1007476
- ↑ Guerra AJ, Zhang O, Bahr CME, Huynh MH, DelProposto J, Brown WC, Wawrzak Z, Koropatkin NM, Carruthers VB. Structural basis of Toxoplasma gondii perforin-like protein 1 membrane interaction and activity during egress. PLoS Pathog. 2018 Dec 4;14(12):e1007476. doi: 10.1371/journal.ppat.1007476., eCollection 2018 Dec. PMID:30513119 doi:http://dx.doi.org/10.1371/journal.ppat.1007476
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