6bxw
From Proteopedia
Crystal structure of Toxoplasma gondii Mitochondrial Association Factor 1 B (MAF1B) in complex with ADPribose
Structural highlights
FunctionMAFB1_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] Publication Abstract from PubMedThe 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[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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