Structural determinants for selective recognition of a lys48-linked polyubiquitin chain by a UBA domain
Structural determinants for selective recognition of a lys48-linked polyubiquitin chain by a UBA domain
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DOI：
10.1016/j.molcel.2005.05.013
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发表时间：
2005-06-10
期刊：
影响因子：
16
通讯作者：
Fushman, D
中科院分区：
文献类型：
--
作者：
Varadan, R;Assfalg, M;Fushman, D
虽然多泛素链信号的功能多样性归因于不同连接链以独特方式与效应蛋白结合的能力，但缺乏这种相互作用的结构模型。在这里，我们利用核磁共振揭示了hHR23A的UBA2结构域选择性识别lys48连接的二和四红素链的结构基础。尽管UBA2与lys48连接的双泛素的相互作用涉及每个泛素单元上与单泛素：UBA复合物中使用的相同的疏水表面，但我们的研究结果表明，lys48连接的双泛素的“封闭”构象对于高亲和力结合至关重要。此外，对lys48连接的双泛素的识别涉及到UBA上一个独特的表位，这允许形成一个三明治状的双泛素：UBA复合物。对UBA-四泛素相互作用的研究表明，UBA与二泛素的这种结合模式与较长的链有关。
Although functional diversity in polyubiquitin chain signaling has been ascribed to the ability of differently linked chains to bind in a distinctive manner to effector proteins, structural models of such interactions have been lacking. Here, we use NMR to unveil the structural basis of selective recognition of Lys48-linked di- and tetraubiquitin chains by the UBA2 domain of hHR23A. Although the interaction of UBA2 with Lys48-linked diubiquitin involves the same hydrophobic surface on each ubiquitin unit as that utilized in monoubiquitin:UBA complexes, our results show how the "closed" conformation of Lys48-linked diubiquitin is crucial for high-affinity binding. Moreover, recognition of Lys48-linked diubiquitin involves a unique epitope on UBA, which allows the formation of a sandwich-like diubiqutin:UBA complex. Studies of the UBA-tetraubiquitin interaction suggest that this mode of UBA binding to diubiquitin is relevant for longer chains.