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| | <StructureSection load='6bxr' size='340' side='right'caption='[[6bxr]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='6bxr' size='340' side='right'caption='[[6bxr]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bxr]] is a 1 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=6BXR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BXR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bxr]] is a 1 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=6BXR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BXR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <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]] 1.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAF1 ([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=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <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=6bxr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bxr OCA], [http://pdbe.org/6bxr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bxr RCSB], [http://www.ebi.ac.uk/pdbsum/6bxr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bxr 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=6bxr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bxr OCA], [https://pdbe.org/6bxr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bxr RCSB], [https://www.ebi.ac.uk/pdbsum/6bxr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bxr ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/MAFB1_TOXGO MAFB1_TOXGO] During host cell infection by tachyzoites, required for tethering the parasitophorous vacuole to the host mitochondria (PubMed:26920761, PubMed:24781109, PubMed:28567444, PubMed:33723040, PubMed:35025629, PubMed:29505111). This process, known as host mitochondrial association (HMA), induces the formation of SPOTs (structures positive for outer mitochondrial membrane (OMM)), a cellular response to OMM stress, which leads to the constitutive shedding of OMM vesicles containing proteins such as mitofusins MFN1 and MFN2, which normally restrict parasite growth (PubMed:35025629). Specifically, binds to the host OMM import receptor TOMM70 to interact with SAMM50, a component of host mitochondrial intermembrane space bridging (MIB) complex (PubMed:28567444, PubMed:33723040, PubMed:35025629). By targeting SAMM50, induces the disassembly of the MIB complex, thereby promoting the formation of SPOTs (PubMed:35025629). Inhibits host TOMM70 import activity (PubMed:35025629). Plays a role in the modulation of the host innate immune response to parasite infection (PubMed:24781109, PubMed:30333181).<ref>PMID:24781109</ref> <ref>PMID:26920761</ref> <ref>PMID:28567444</ref> <ref>PMID:29505111</ref> <ref>PMID:30333181</ref> <ref>PMID:33723040</ref> <ref>PMID:35025629</ref> |
| - | The Toxoplasma gondii locus mitochondrial association factor 1 (MAF1) encodes multiple paralogs, some of which mediate host mitochondrial association (HMA). Previous work showed that HMA was a trait that arose in T. gondii through neofunctionalization of an ancestral MAF1 ortholog. Structural analysis of HMA-competent and incompetent MAF1 paralogs (MAF1b and MAF1a, respectively) revealed that both paralogs harbor an ADP ribose binding macro-domain, with comparatively low (micromolar) affinity for ADP ribose. Replacing the 16 C-terminal residues of MAF1b with those of MAF1a abrogated HMA, and we also show that only three residues in the C-terminal helix are required for MAF1-mediated HMA. Importantly these same three residues are also required for the in vivo growth advantage conferred by MAF1b, providing a definitive link between in vivo proliferation and manipulation of host mitochondria. Co-immunoprecipitation assays reveal that the ability to interact with the mitochondrial MICOS complex is shared by HMA-competent and incompetent MAF1 paralogs and mutants. The weak ADPr coordination and ability to interact with the MICOS complex shared between divergent paralogs may represent modular ancestral functions for this tandemly expanded and diversified T. gondii locus.
| + | |
| - | | + | |
| - | A Toxoplasma gondii locus required for the direct manipulation of host mitochondria has maintained multiple ancestral functions.,Blank ML, Parker ML, Ramaswamy R, Powell CJ, English ED, Adomako-Ankomah Y, Pernas LF, Workman SD, Boothroyd JC, Boulanger MJ, Boyle JP Mol Microbiol. 2018 Jun;108(5):519-535. doi: 10.1111/mmi.13947. Epub 2018 Apr 11. PMID:29505111<ref>PMID:29505111</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div> | + | |
| - | <div class="pdbe-citations 6bxr" style="background-color:#fffaf0;"></div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Toxgo]] | + | [[Category: Toxoplasma gondii]] |
| - | [[Category: Boulanger, M J]] | + | [[Category: Boulanger MJ]] |
| - | [[Category: Parker, M L]] | + | [[Category: Parker ML]] |
| - | [[Category: Ramaswamy, R]] | + | [[Category: Ramaswamy R]] |
| - | [[Category: Adpribose]]
| + | |
| - | [[Category: Macro domain]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Neofunctionalize]]
| + | |
| Structural highlights
Function
MAFB1_TOXGO During host cell infection by tachyzoites, required for tethering the parasitophorous vacuole to the host mitochondria (PubMed:26920761, PubMed:24781109, PubMed:28567444, PubMed:33723040, PubMed:35025629, PubMed:29505111). This process, known as host mitochondrial association (HMA), induces the formation of SPOTs (structures positive for outer mitochondrial membrane (OMM)), a cellular response to OMM stress, which leads to the constitutive shedding of OMM vesicles containing proteins such as mitofusins MFN1 and MFN2, which normally restrict parasite growth (PubMed:35025629). Specifically, binds to the host OMM import receptor TOMM70 to interact with SAMM50, a component of host mitochondrial intermembrane space bridging (MIB) complex (PubMed:28567444, PubMed:33723040, PubMed:35025629). By targeting SAMM50, induces the disassembly of the MIB complex, thereby promoting the formation of SPOTs (PubMed:35025629). Inhibits host TOMM70 import activity (PubMed:35025629). Plays a role in the modulation of the host innate immune response to parasite infection (PubMed:24781109, PubMed:30333181).[1] [2] [3] [4] [5] [6] [7]
References
- ↑ Pernas L, Adomako-Ankomah Y, Shastri AJ, Ewald SE, Treeck M, Boyle JP, Boothroyd JC. Toxoplasma effector MAF1 mediates recruitment of host mitochondria and impacts the host response. PLoS Biol. 2014 Apr 29;12(4):e1001845. PMID:24781109 doi:10.1371/journal.pbio.1001845
- ↑ Adomako-Ankomah Y, English ED, Danielson JJ, Pernas LF, Parker ML, Boulanger MJ, Dubey JP, Boyle JP. Host Mitochondrial Association Evolved in the Human Parasite Toxoplasma gondii via Neofunctionalization of a Gene Duplicate. Genetics. 2016 May;203(1):283-98. PMID:26920761 doi:10.1534/genetics.115.186270
- ↑ Kelly FD, Wei BM, Cygan AM, Parker ML, Boulanger MJ, Boothroyd JC. Toxoplasma gondii MAF1b Binds the Host Cell MIB Complex To Mediate Mitochondrial Association. mSphere. 2017 May 24;2(3):e00183-17. PMID:28567444 doi:10.1128/mSphere.00183-17
- ↑ Blank ML, Parker ML, Ramaswamy R, Powell CJ, English ED, Adomako-Ankomah Y, Pernas LF, Workman SD, Boothroyd JC, Boulanger MJ, Boyle JP. A Toxoplasma gondii locus required for the direct manipulation of host mitochondria has maintained multiple ancestral functions. Mol Microbiol. 2018 Jun;108(5):519-535. doi: 10.1111/mmi.13947. Epub 2018 Apr 11. PMID:29505111 doi:http://dx.doi.org/10.1111/mmi.13947
- ↑ English ED, Boyle JP. Impact of Engineered Expression of Mitochondrial Association Factor 1b on Toxoplasma gondii Infection and the Host Response in a Mouse Model. mSphere. 2018 Oct 17;3(5):e00471-18. PMID:30333181 doi:10.1128/mSphere.00471-18
- ↑ Blank ML, Xia J, Morcos MM, Sun M, Cantrell PS, Liu Y, Zeng X, Powell CJ, Yates N, Boulanger MJ, Boyle JP. Toxoplasma gondii association with host mitochondria requires key mitochondrial protein import machinery. Proc Natl Acad Sci U S A. 2021 Mar 23;118(12):e2013336118. PMID:33723040 doi:10.1073/pnas.2013336118
- ↑ Li X, Straub J, Medeiros TC, Mehra C, den Brave F, Peker E, Atanassov I, Stillger K, Michaelis JB, Burbridge E, Adrain C, Münch C, Riemer J, Becker T, Pernas LF. Mitochondria shed their outer membrane in response to infection-induced stress. Science. 2022 Jan 14;375(6577):eabi4343. PMID:35025629 doi:10.1126/science.abi4343
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