Structural basis for distinct roles of Lys63- and Lys48-linked polyubiquitin chains
Structural basis for distinct roles of Lys63- and Lys48-linked polyubiquitin chains
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DOI：
10.1111/j.1365-2443.2004.00780.x
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发表时间：
2004-10-01
期刊：
影响因子：
2.1
通讯作者：
Shirakawa, M
中科院分区：
文献类型：
--
作者：
Tenno, T;Fujiwara, K;Shirakawa, M
泛素化是一种将单个或多个泛素分子附着在蛋白质上的修饰，它具有控制多种细胞过程的信号功能。迄今为止，多泛素链的两种主要形式已被功能表征，其中异肽键连接涉及Lys48或Lys63。lys48连接的多泛素标记主要用于靶向蛋白酶体降解的蛋白质，而lys63连接的多泛素化已与许多不依赖于蛋白酶体降解信号传导的细胞事件相关。显然，多泛素链的连接特异性构象对这些细胞功能很重要，但区分Lys48-和lys63 -链的结构基础仍然难以捉摸。在这里，我们报道了核磁共振和小角度x射线散射（SAXS）对Lys63-和lys48连接的二-和四红素链的亚基间界面和构象的研究。我们的研究结果表明，与lys48链相比，lys63链是细长的分子，没有稳定的非共价亚基界面，因此与lys48链具有完全不同的构象。
Ubiquitination, a modification in which single or multiple ubiquitin molecules are attached to a protein, serves as a signalling function that controls a wide variety of cellular processes. To date, two major forms of polyubiquitin chain have been functionally characterized, in which the isopeptide bond linkages involve Lys48 or Lys63. Lys48-linked polyubiquitin tagging is mostly used to target proteins for degradation by the proteasome, whereas Lys63-linked polyubiquitination has been linked to numerous cellular events that do not rely on degradative signalling via the proteasome. Apparently linkage-specific conformations of polyubiquitin chains are important for these cellular functions, but the structural bases distinguishing Lys48- and Lys63-linked chains remain elusive. Here, we report NMR and small-angle X-ray scattering (SAXS) studies on the intersubunit interfaces and conformations of Lys63- and Lys48-linked di- and tetraubiquitin chains. Our results indicate that, in marked contrast to Lys48-linked chains, Lys63-linked chains are elongated molecules with no stable non-covalent intersubunit interfaces and thus adopt a radically different conformation from that of Lys48-linked chains.