转运所需的内体分选复合物(ESCRT)在真核细胞的膜结合区室之间的蛋白质分选中起关键作用。许多ESCRT组件的同源物在各种古细菌中都可以识别,尤其是在Asgardarcheota,目前被认为包括真核生物最近亲的古门,但不是细菌。我们使用Vps4ATPase(ESCRTIV)的系统发育树作为支架,并使用敏感的蛋白质序列分析和结构模型比较来鉴定以前未知的ESCRT蛋白,对古细菌中的ESCRT蛋白同源物进行了全面搜索,并重建了ESCRT进化。在Asgard外部的古细菌中确定了几组不同的ESCRT系统,包括结构上类似于ESCRT-I和ESCRT-II的蛋白质,和其他一些参与真核生物蛋白质分选的结构域,表明这些成分的早期起源。此外,在Thermoproteales中鉴定出CdvA蛋白的远缘同源物,这些同源物可能是这些古细菌中未表征的细胞分裂系统的组成部分。我们提出了一种进化方案,用于从祖先的积木中起源真核生物和AsgardESCRT复合物,即,VPS4ATPase,ESCRT-III组件,wH(有翼螺旋-转弯-螺旋折叠),也可能是卷曲螺旋,和类似Vps28的域。最后一个古细菌共同祖先可能包含一个复杂的ESCRT系统,该系统涉及蛋白质分选。随后的演变涉及简化,就像在TACK超门中一样,其中ESCRT被选择用于细胞分裂,或复杂,如阿斯加德考古。在Asgardarcheota,ESCRT与以前被认为是真核生物特征的泛素系统之间的联系已经建立.重要所有真核细胞都具有复杂的胞内膜组织。转运所需的内体分选复合物(ESCRT)在膜重塑中起着核心作用,这对于真核生物的细胞功能至关重要。最近,已经证明阿斯加德古细菌,包括真核生物已知近亲的古门,编码ESCRT系统的许多组件的同源物。我们采用蛋白质序列和结构比较来重建古细菌中ESCRT系统的进化,并鉴定了几个先前未知的ESCRT亚基同源物,其中一些可以预测参与细胞分裂。这种重建的结果表明,最后一个古细菌共同祖先已经编码了一个复杂的ESCRT系统,该系统涉及蛋白质分选。在阿斯加德古细菌中,ESCRT系统朝着更复杂的方向发展,特别是,建立了ESCRT与泛素系统之间的联系,该系统以前被认为是真核生物的特征.
Endosomal sorting complexes required for transport (ESCRT) play key roles in protein sorting between membrane-bounded compartments of eukaryotic cells. Homologs of many ESCRT components are identifiable in various groups of archaea, especially in Asgardarchaeota, the archaeal phylum that is currently considered to include the closest relatives of eukaryotes, but not in bacteria. We performed a comprehensive search for ESCRT protein homologs in archaea and reconstructed ESCRT evolution using the phylogenetic tree of Vps4 ATPase (ESCRT IV) as a scaffold and using sensitive protein sequence analysis and comparison of structural models to identify previously unknown ESCRT proteins. Several distinct groups of ESCRT systems in archaea outside of Asgard were identified, including proteins structurally similar to ESCRT-I and ESCRT-II, and several other domains involved in protein sorting in eukaryotes, suggesting an early origin of these components. Additionally, distant homologs of CdvA proteins were identified in Thermoproteales which are likely components of the uncharacterized cell division system in these archaea. We propose an evolutionary scenario for the origin of eukaryotic and Asgard ESCRT complexes from ancestral building blocks, namely, the Vps4 ATPase, ESCRT-III components, wH (winged helix-turn-helix fold) and possibly also coiled-coil, and Vps28-like domains. The last archaeal common ancestor likely encompassed a complex ESCRT system that was involved in protein sorting. Subsequent evolution involved either simplification, as in the TACK superphylum, where ESCRT was co-opted for cell division, or complexification as in Asgardarchaeota. In Asgardarchaeota, the connection between ESCRT and the ubiquitin system that was previously considered a eukaryotic signature was already established.IMPORTANCEAll eukaryotic cells possess complex intracellular membrane organization. Endosomal sorting complexes required for transport (ESCRT) play a central role in membrane remodeling which is essential for cellular functionality in eukaryotes. Recently, it has been shown that Asgard archaea, the archaeal phylum that includes the closest known relatives of eukaryotes, encode homologs of many components of the ESCRT systems. We employed protein sequence and structure comparisons to reconstruct the evolution of ESCRT systems in archaea and identified several previously unknown homologs of ESCRT subunits, some of which can be predicted to participate in cell division. The results of this reconstruction indicate that the last archaeal common ancestor already encoded a complex ESCRT system that was involved in protein sorting. In Asgard archaea, ESCRT systems evolved toward greater complexity, and in particular, the connection between ESCRT and the ubiquitin system that was previously considered a eukaryotic signature was established.