Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, 84105, Israel.
National Institute for Biotechnology in the Negev (NIBN), Ben-Gurion University of the Negev, Beer Sheva, 84105, Israel.
ISME J. 2023 Jan;17(1):117-129. doi: 10.1038/s41396-022-01328-2. Epub 2022 Oct 12.
The archaeal Asgard superphylum currently stands as the most promising prokaryotic candidate, from which eukaryotic cells emerged. This unique superphylum encodes for eukaryotic signature proteins (ESP) that could shed light on the origin of eukaryotes, but the properties and function of these proteins is largely unresolved. Here, we set to understand the function of an Asgard archaeal protein family, namely the ESCRT machinery, that is conserved across all domains of life and executes basic cellular eukaryotic functions, including membrane constriction during cell division. We find that ESCRT proteins encoded in Loki archaea, express in mammalian and yeast cells, and that the Loki ESCRT-III protein, CHMP4-7, resides in the eukaryotic nucleus in both organisms. Moreover, Loki ESCRT-III proteins associated with chromatin, recruited their AAA-ATPase VPS4 counterpart to organize in discrete foci in the mammalian nucleus, and directly bind DNA. The human ESCRT-III protein, CHMP1B, exhibited similar nuclear properties and recruited both human and Asgard VPS4s to nuclear foci, indicating interspecies interactions. Mutation analysis revealed a role for the N terminal region of ESCRT-III in mediating these phenotypes in both human and Asgard ESCRTs. These findings suggest that ESCRT proteins hold chromatin binding properties that were highly preserved through the billion years of evolution separating Asgard archaea and humans. The conserved chromatin binding properties of the ESCRT membrane remodeling machinery, reported here, may have important implications for the origin of eukaryogenesis.
古菌的 Asgard 超界目前是最有希望的原核候选者，真核细胞就是从这里起源的。这个独特的超界编码了真核生物特征蛋白 (ESP)，这可能有助于我们了解真核生物的起源，但这些蛋白的性质和功能在很大程度上仍未得到解决。在这里，我们着手研究 Asgard 古菌蛋白家族的功能，即 ESCRT 机器，它在所有生命领域中都保守存在，并执行基本的真核细胞功能，包括在细胞分裂过程中膜的收缩。我们发现 Loki 古菌编码的 ESCRT 蛋白在哺乳动物和酵母细胞中表达，并且 Loki 的 ESCRT-III 蛋白 CHMP4-7 存在于这两种生物的真核核内。此外，与染色质结合的 Loki ESCRT-III 蛋白招募其 AAA-ATPase VPS4 对应物在哺乳动物核内形成离散焦点，并直接结合 DNA。人类的 ESCRT-III 蛋白 CHMP1B 表现出类似的核性质，并招募了人类和 Asgard 的 VPS4 形成核焦点，表明存在种间相互作用。突变分析表明，ESCRT-III 的 N 端区域在介导人类和 Asgard ESCRT 的这些表型中起作用。这些发现表明，ESCRT 蛋白具有染色质结合特性，这些特性在 Asgard 古菌和人类之间的数十亿年进化中得到了高度保留。这里报道的 ESCRT 膜重塑机制的保守染色质结合特性，可能对真核生物起源具有重要意义。
