Molecular phylogeny of a RING E3 ubiquitin ligase, conserved in eukaryotic cells and dominated by homologous components, the muskelin/RanBPM/CTLH complex.
Molecular phylogeny of a RING E3 ubiquitin ligase, conserved in eukaryotic cells and dominated by homologous components, the muskelin/RanBPM/CTLH complex.
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DOI：
10.1371/journal.pone.0075217
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Adams JC
中科院分区：
文献类型：
--
作者：
Francis O;Han F;Adams JC
泛素化是真核细胞中调节信号传导和蛋白质周转的重要翻译后修饰。泛素化的特异性由泛素E3连接酶驱动，其中许多仍然知之甚少。其中之一是哺乳动物muskelin/RanBP 9/CTLH复合物，其包括八种蛋白质，其中五种（RanBP 9/RanBPM、TWA 1、MAEA、Rmnd 5和muskelin）共享结构域结构的惊人相似性，并且涉及细胞组织的调节。在芽殖酵母中，同源的GID复合物起下调芽殖形成的作用。在这两种复合物中，Rmnd 5/GID 2对应于RING泛素连接酶。为了更好地了解E3连接酶系统，我们对相关组分进行了分子系统发育和序列分析。TWA 1、Rmnd 5、MAEA和WDR 26在所有真核生物超群中是保守的，尽管WDR 26在根瘤菌中未被鉴定。RanBPM在挖掘者和一些亚谱系中是不存在的。armc 8和c17 orf 39在单粒种中均有表达，但在双粒种中仅在绿色植物纲和O.在小槽内的三叶草。马斯克林只存在于后孔兽中。对RanBPM、TWA 1、MAEA和Rmnd 5的共有LisH和CTLH结构域的系统发育和序列分析显示，Rmnd 5和MAEA、RanBPM和TWA 1之间的保守残基关系更密切，且分布更广。Rmnd 5和MAEA也通过保守的变异RING结构域的存在而相关。检查N-或C-末端结构域缺失如何改变哺乳动物细胞中每种蛋白质的亚细胞定位，确定了LisH结构域对蛋白质定位或折叠/稳定性的不同贡献。总之，所有的组件，除了muskelin推断已存在于最后的真核生物共同祖先。这种连接酶复合物在不同真核细胞谱系中的多样性可能是由于RanBPM的明显快速进化，对WDR 26，Armc 8或c17 orf 39的不同要求，以及后突动物中的muskelin作为RanBPM结合蛋白的起源。
Ubiquitination is an essential post-translational modification that regulates signalling and protein turnover in eukaryotic cells. Specificity of ubiquitination is driven by ubiquitin E3 ligases, many of which remain poorly understood. One such is the mammalian muskelin/RanBP9/CTLH complex that includes eight proteins, five of which (RanBP9/RanBPM, TWA1, MAEA, Rmnd5 and muskelin), share striking similarities of domain architecture and have been implicated in regulation of cell organisation. In budding yeast, the homologous GID complex acts to down-regulate gluconeogenesis. In both complexes, Rmnd5/GID2 corresponds to a RING ubiquitin ligase. To better understand this E3 ligase system, we conducted molecular phylogenetic and sequence analyses of the related components. TWA1, Rmnd5, MAEA and WDR26 are conserved throughout all eukaryotic supergroups, albeit WDR26 was not identified in Rhizaria. RanBPM is absent from Excavates and from some sub-lineages. Armc8 and c17orf39 were represented across unikonts but in bikonts were identified only in Viridiplantae and in O. trifallax within alveolates. Muskelin is present only in Opisthokonts. Phylogenetic and sequence analyses of the shared LisH and CTLH domains of RanBPM, TWA1, MAEA and Rmnd5 revealed closer relationships and profiles of conserved residues between, respectively, Rmnd5 and MAEA, and RanBPM and TWA1. Rmnd5 and MAEA are also related by the presence of conserved, variant RING domains. Examination of how N- or C-terminal domain deletions alter the sub-cellular localisation of each protein in mammalian cells identified distinct contributions of the LisH domains to protein localisation or folding/stability. In conclusion, all components except muskelin are inferred to have been present in the last eukaryotic common ancestor. Diversification of this ligase complex in different eukaryotic lineages may result from the apparently fast evolution of RanBPM, differing requirements for WDR26, Armc8 or c17orf39, and the origin of muskelin in opisthokonts as a RanBPM-binding protein.
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影响因子：
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