6bxr

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

1. ↑ 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
2. ↑ 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
3. ↑ 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
4. ↑ 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
5. ↑ 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
6. ↑ 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
7. ↑ 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