Insights into the evolution of regulated actin dynamics via characterization of primitive gelsolin/cofilin proteins from Asgard archaea
Insights into the evolution of regulated actin dynamics via characterization of primitive gelsolin/cofilin proteins from Asgard archaea
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DOI：
10.1073/pnas.200199049167117
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发表时间：
2020-08-18
影响因子：
11.1
通讯作者：
Robinson, Robert C.
中科院分区：
文献类型：
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作者：
Akil, Caner;Tran, Linh T.;Robinson, Robert C.
阿斯加德古菌基因组包含潜在的真核生物样基因，为真核生物的进化提供了有趣的见解。真核细胞肌动蛋白的聚合/解聚循环在许多过程中，包括膜重塑，提供力和结构是至关重要的。一般来说，Asgard基因组编码两类肌动蛋白调节蛋白，profi-lin和凝溶胶蛋白。Asgard profilins被证明调节肌动蛋白丝成核。在这里，我们确定肌动蛋白丝切断，帽，退火和捆绑，和单体螯合活动的凝溶胶蛋白从Thorarchaeota（Thor），这完成了一个真核生物样的肌动蛋白解聚周期，并指示复杂的肌动蛋白细胞骨架的调节Asgard生物。Thor凝溶胶蛋白在其他Asgard古菌中具有同源物，并且包含原型凝溶胶蛋白结构域的一个或两个拷贝。这似乎是一个初始的前真核基因复制事件的记录，因为真核凝溶胶蛋白通常包含三到六个结构域。这些蛋白质与哺乳动物肌动蛋白复合物的X-射线结构揭示了与人凝溶胶蛋白或cofilin与肌动蛋白的第一结构域类似的相互作用。Asgard凝溶胶蛋白是双结构域而非单结构域，含有钙离子结合位点，表现为钙离子控制的活性。哺乳动物细胞中双域凝溶胶蛋白的表达增强了离子霉素触发的钙释放中肌动蛋白丝的分解。这种功能演示，在细胞水平上，提供了钙控制的Asgard肌动蛋白细胞骨架的证据，表明钙调节肌动蛋白细胞骨架早于真核生物。在真核生物中，动态成束的肌动蛋白丝负责形成丝状伪足和微绒毛。通过相关性，我们推测，从Lokiarchaeota细胞体观察到的突起的形成可能涉及凝溶胶蛋白调节的肌动蛋白结构。
Asgard archaea genomes contain potential eukaryotic-like genes that provide intriguing insight for the evolution of eukaryotes. The eukaryotic actin polymerization/depolymerization cycle is crit-ical for providing force and structure in many processes, including membrane remodeling. In general, Asgard genomes encode two classes of actin-regulating proteins from sequence analysis, profi-lins and gelsolins. Asgard profilins were demonstrated to regulate actin filament nucleation. Here, we identify actin filament sever-ing, capping, annealing and bundling, and monomer sequestration activities by gelsolin proteins from Thorarchaeota (Thor), which complete a eukaryotic-like actin depolymerization cycle, and indi-cate complex actin cytoskeleton regulation in Asgard organisms. Thor gelsolins have homologs in other Asgard archaea and com-prise one or two copies of the prototypical gelsolin domain. This appears to be a record of an initial preeukaryotic gene duplication event, since eukaryotic gelsolins are generally comprise three to six domains. X-ray structures of these proteins in complex with mammalian actin revealed similar interactions to the first domain of human gelsolin or cofilin with actin. Asgard two-domain, but not one-domain, gelsolins contain calcium-binding sites, which is manifested in calcium-controlled activities. Expression of two-domain gelsolins in mammalian cells enhanced actin filament dis-assembly on ionomycin-triggered calcium release. This functional demonstration, at the cellular level, provides evidence for a calcium-controlled Asgard actin cytoskeleton, indicating that the calcium-regulated actin cytoskeleton predates eukaryotes. In eu-karyotes, dynamic bundled actin filaments are responsible for shaping filopodia and microvilli. By correlation, we hypothe-size that the formation of the protrusions observed from Lokiarchaeota cell bodies may involve the gelsolin-regulated actin structures.