Catic André, Sun Zhen-Yu J, Ratner Daniel M, Misaghi Shahram, Spooner Eric, Samuelson John, Wagner Gerhard, Ploegh Hidde L
Department of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
EMBO J. 2007 Jul 25;26(14):3474-83. doi: 10.1038/sj.emboj.7601772. Epub 2007 Jun 28.
Encoded by a multigene family, ubiquitin is expressed in the form of three precursor proteins, two of which are fusions to the ribosomal subunits S27a and L40. Ubiquitin assists in ribosome biogenesis and also functions as a post-translational modifier after its release from S27a or L40. However, several species do not conserve the ribosomal ubiquitin domains. We report here the solution structure of a distant variant of ubiquitin, found at the N-terminus of S27a in Giardia lamblia, referred to as GlUb(S27a). Despite the considerable evolutionary distance that separates ubiquitin from GlUb(S27a), the structure of GlUb(S27a) is largely identical to that of ubiquitin. The variant domain remains attached to S27a and is part of the assembled holoribosome. Thus, conservation of tertiary structure suggests a role of this variant as a chaperone, while conservation of the primary structure--necessary for ubiquitin's function as a post-translational modifier--is no longer required. Based on these observations, we propose a model to explain the origin of the widespread ubiquitin superfold in eukaryotes.
泛素由一个多基因家族编码，以三种前体蛋白的形式表达，其中两种是与核糖体亚基S27a和L40的融合蛋白。泛素协助核糖体生物合成，并且在从S27a或L40释放后还作为翻译后修饰因子发挥作用。然而，几种物种并不保留核糖体泛素结构域。我们在此报告了一种泛素远缘变体的溶液结构，它存在于蓝氏贾第鞭毛虫S27a的N端，称为GlUb(S27a)。尽管泛素与GlUb(S27a)之间存在相当大的进化距离，但GlUb(S27a)的结构与泛素的结构基本相同。该变体结构域仍与S27a相连，并且是组装好的完整核糖体的一部分。因此，三级结构的保守性表明该变体作为伴侣蛋白发挥作用，而泛素作为翻译后修饰因子功能所必需的一级结构的保守性则不再需要。基于这些观察结果，我们提出了一个模型来解释真核生物中广泛存在的泛素超折叠的起源。
