A Toxoplasma gondii locus required for the direct manipulation of host mitochondria has maintained multiple ancestral functions
A Toxoplasma gondii locus required for the direct manipulation of host mitochondria has maintained multiple ancestral functions
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DOI：
10.1111/mmi.13947
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发表时间：
2018-06-01
影响因子：
3.6
通讯作者：
Boyle, Jon P.
中科院分区：
文献类型：
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作者：
Blank, Matthew L.;Parker, Michelle L.;Boyle, Jon P.
弓形虫线粒体关联因子1(MAF1)编码多个并列基因，其中一些参与介导宿主线粒体联合(HMA)。以前的工作表明，HMA是弓形虫通过对其祖先MAF1同源基因进行新功能化而产生的一种特征。对HMA活性和非活性MAF1配基的结构分析表明，这两个配基都含有ADP核糖结合的大结构域，与ADP核糖的亲和力较低(微摩尔)。用MAF1a的16个C-末端残基取代MAF1b的16个C-末端残基，我们还发现MAF1介导的HMA只需要C-末端螺旋上的3个残基。重要的是，这三个相同的残基也是MAF1b赋予体内生长优势所必需的，提供了体内增殖和宿主线粒体操纵之间的明确联系。免疫共沉淀分析表明，与线粒体MICOS复合体相互作用的能力是由HMA功能和非功能MAF1类似基因和突变体共享的。在不同的对虾之间，弱的ADPr协调和与MICOS复合体相互作用的能力可能代表了这个简单扩展和多样化的弓形虫基因座的模块化祖先功能。
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.