Anjum Rana S, Bray Sian M, Blackwood John K, Kilkenny Mairi L, Coelho Matthew A, Foster Benjamin M, Li Shurong, Howard Julie A, Pellegrini Luca, Albers Sonja-Verena, Deery Michael J, Robinson Nicholas P
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.
Department of Biochemistry and Cambridge Systems Biology Centre, Cambridge Centre for Proteomics, Cambridge CB2 1QR, UK.
Nat Commun. 2015 Sep 8;6:8163. doi: 10.1038/ncomms9163.
In eukaryotes, the covalent attachment of ubiquitin chains directs substrates to the proteasome for degradation. Recently, ubiquitin-like modifications have also been described in the archaeal domain of life. It has subsequently been hypothesized that ubiquitin-like proteasomal degradation might also operate in these microbes, since all archaeal species utilize homologues of the eukaryotic proteasome. Here we perform a structural and biochemical analysis of a ubiquitin-like modification pathway in the archaeon Sulfolobus acidocaldarius. We reveal that this modifier is homologous to the eukaryotic ubiquitin-related modifier Urm1, considered to be a close evolutionary relative of the progenitor of all ubiquitin-like proteins. Furthermore we demonstrate that urmylated substrates are recognized and processed by the archaeal proteasome, by virtue of a direct interaction with the modifier. Thus, the regulation of protein stability by Urm1 and the proteasome in archaea is likely representative of an ancient pathway from which eukaryotic ubiquitin-mediated proteolysis has evolved.
在真核生物中，泛素链的共价连接将底物导向蛋白酶体进行降解。最近，在古菌生命域中也发现了类泛素修饰。随后有人推测，类泛素蛋白酶体降解可能也在这些微生物中起作用，因为所有古菌物种都利用真核蛋白酶体的同源物。在此，我们对嗜热栖热菌中的类泛素修饰途径进行了结构和生化分析。我们发现这种修饰物与真核类泛素相关修饰物Urm1同源，Urm1被认为是所有类泛素蛋白祖先的近亲。此外，我们证明，通过与修饰物的直接相互作用，古菌蛋白酶体能够识别并处理经泛素样修饰的底物。因此，古菌中Urm1和蛋白酶体对蛋白质稳定性的调控可能代表了一种古老的途径，真核生物中泛素介导的蛋白水解作用就是从这一途径进化而来的。
