Archaeal roots of intramembrane aspartyl protease siblings signal peptide peptidase and presenilin
Archaeal roots of intramembrane aspartyl protease siblings signal peptide peptidase and presenilin
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DOI：
10.1002/prot.26009
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发表时间：
2020-09
期刊：
影响因子：
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通讯作者：
Priyam Raut;J. Glass;R. Lieberman
中科院分区：
文献类型：
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作者：
Priyam Raut;J. Glass;R. Lieberman
信号肽帮助新合成的蛋白质到达细胞膜或被分泌。作为人类免疫应答和监视的关键生物学过程的一部分，并且与疾病（例如阿尔茨海默病）相关，残余信号肽和其他跨膜区段被膜内乙酰基蛋白酶（IAP）酶家族蛋白水解。在这里，我们在整个生命树中鉴定了IAP直系同源物。除了真核生物之外，IAP还在来自广泛环境的代谢多样性古细菌中编码。我们发现了三个不同的古细菌IAP分支：（a）Euryarchaeota（例如，嗜盐菌目，产甲烷甲烷菌目和甲烷微菌目，海洋Poseidoniales，嗜酸热胞浆菌目，超嗜热古球菌属），(b)DPANN，和（c）Bathyarchaeota，Crenarchaeota和Asgard。IAP也存在于候选门辐射的未培养成员的细菌基因组中，这可能是由于来自DPANN古细菌谱系的水平基因转移。对来自古细菌和细菌的IAP中的催化基序YD... GXGD（其中X是任何氨基酸）的序列分析揭示了Lokiarchaeota中的WD和X位置的许多残基类型。嗜盐古菌中的基因邻域分析显示IAP基因靠近corrinoid转运蛋白（btuCDF基因）。在海洋Euryarchaeota中，在IAP基因的N末端发现了一个推定的BtuF-样结构域，表明这些IAP在金属离子辅因子或其他营养物质清除中的作用。有趣的是，真核生物IAP家族成员似乎是从Euryarchaeota或Asgard archaea进化而来的。两者合计，我们的系统发育和生物信息学分析应提示实验，以探测IAP在原核分泌的生物学作用。
Signal peptides help newly synthesized proteins reach the cell membrane or be secreted. As part of a biological process key to immune response and surveillance in humans, and associated with diseases, for example, Alzheimer, remnant signal peptides and other transmembrane segments are proteolyzed by the intramembrane aspartyl protease (IAP) enzyme family. Here, we identified IAP orthologs throughout the tree of life. In addition to eukaryotes, IAPs are encoded in metabolically diverse archaea from a wide range of environments. We found three distinct clades of archaeal IAPs: (a) Euryarchaeota (eg, halophilic Halobacteriales, methanogenic Methanosarcinales and Methanomicrobiales, marine Poseidoniales, acidophilic Thermoplasmatales, hyperthermophilic Archaeoglobus spp.), (b) DPANN, and (c) Bathyarchaeota, Crenarchaeota, and Asgard. IAPs were also present in bacterial genomes from uncultivated members of Candidate Phylum Radiation, perhaps due to horizontal gene transfer from DPANN archaeal lineages. Sequence analysis of the catalytic motif YD…GXGD (where X is any amino acid) in IAPs from archaea and bacteria reveals WD in Lokiarchaeota and many residue types in the X position. Gene neighborhood analysis in halophilic archaea shows IAP genes near corrinoid transporters (btuCDF genes). In marine Euryarchaeota, a putative BtuF‐like domain is found in N‐terminus of the IAP gene, suggesting a role for these IAPs in metal ion cofactor or other nutrient scavenging. Interestingly, eukaryotic IAP family members appear to have evolved either from Euryarchaeota or from Asgard archaea. Taken together, our phylogenetic and bioinformatics analysis should prompt experiments to probe the biological roles of IAPs in prokaryotic secretomes.